Interleukin Research Articles

Prognostic Value of Serum Interleukin-37 in Patients with Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is prominently characterized by uncontrolled inflammation and high mortality. The effect of interleukin-37 (IL-37) on the prognosis of ARDS remains unclear. This prospective cohort study detected and analyzed serum IL-37 levels on day 1 (baseline) in 128 patients with ARDS and 40healthy controls, and on day 7 in patients with ARDS. Clinical and laboratory parameters were assayed. Survival status was tracked within 28-d of enrollment. BaselineIL-37 concentration was lower in non-survivors (135.00 [87.75, 198.75] pg/mL) than in survivors (250.50 [173.25, 382.75] pg/mL) (p < .05). Non-survivors displayed a greater reduction in IL-37 levels from day 1-7 than survivors (49.87% vs. 40.09%) (p < .05). Baseline IL-37 levels were negatively associated with C-reactive protein, procalcitonin, and IL-6 levels. The area under the receiver operating characteristic curve of the baseline level and percentage decline in IL-37 was 0.755 and 0.809, respectively, for predicting 28-d mortality. Combining IL-37 with the acute physiology and chronic health evaluation II score further improved mortality prediction capability. Patients with ARDS with low IL-37 concentrations (<143.00 pg/mL) or a high percentage decline (≥44.76%) had a poorer survival rate than those with a high concentration or low percentage decline. The baseline IL-37 level and percentage decline independently predicted mortality in a univariate Cox regression model (p < .05). A low IL-37 level or significantly declining rate predicts higher 28-d mortality in patients with ARDS, indicating that IL-37 may be a promising prognostic biomarker.

Evaluation of IL-8 and IL-6 levels in gingival crevicular fluid of individuals undergoing clear aligner therapy.

To compare short-term changes in the levels of interleukin-8 (IL-8) and interleukin-6 (IL-6) in the gingival crevicular fluid (GCF) of individuals undergoing orthodontic treatment with clear aligners. This study included 15 individuals. Each patient used clear aligners designed not to cause tooth movement in the GCF sampled teeth, to be changed every 10 days. GCF samples were collected from teeth 16 (upper right first molar) and 31 (lower left central incisor) at baseline and after the procedure at the first hour, third, seventh, 14th, and 21st days. In addition, clinical periodontal parameters for the full mouth and the teeth from which GCF was collected were recorded initially and on the 21st day. A statistically significant difference was observed between the levels of IL-8 before the procedure, on the third and seventh days, and on the 21st day (P < .01). The increase in IL-6 levels on the 14th and 21st days was significantly different compared to the levels before the procedure (P < .01). A positive correlation was detected between IL-8 and IL-6 levels at the first hour, a negative correlation on the third day, and a lower level of positive correlation on the seventh, 14th, and 21st days. Within 21 days, the levels of IL-8 and IL-6 significantly increased in individuals undergoing orthodontic treatment with clear aligners. Within the limits of this study, the clear aligner material may affect the levels of IL-8 and IL-6 in the GCF.

Molecular docking and invitro evaluation of glucosamine sulfate targeting MMP-3, MMP-9, and IL-4 for potential osteoarthritis treatment.

This study intended to investigate the potential of glucosamine sulfate (GS) as an inhibitor of genes involved in osteoarthritis (OA) development. Despite GS is often used for OA treatment due to its cartilage preservation and minimum side effects, the molecular mechanism behind its interactions remains unknown. Molecular docking was conducted to analyze the interactions between glucosamine sulfate and genes associated with OA such as matrix metalloproteinase-3 (MMP-3), MMP-9, and interleukin-4 (IL-4). Additionally, a cell viability assay using RAW 264.7 cells was performed to evaluate the toxicity of glucosamine sulfate at various concentrations. Molecular docking results revealed that glucosamine sulfate has a good binding affinity and stable interactions with MMP-3, MMP-9, and IL-4, indicating that it may have inhibitory effects on targeted genes. Nevertheless, the cell viability assay analysis demonstrated that glucosamine sulfate had considerable toxic effects in RAW 264.7 cells at highest concentrations. Glucosamine sulfate exhibited stable molecular interactions with genes associated to OA development. However, GS toxicity at high concentrations necessitates future research studies to optimize dosing and assess its therapeutic safety in OA treatment.

Advancing immunosuppression in liver transplantation: the role of regulatory T cells in immune modulation and graft tolerance.

Prolonged immunosuppressive therapy in liver transplantation (LT) is associated with significant adverse effects, such as nephrotoxicity, metabolic complications, and heightened risk of infection or malignancy. Regulatory T cells (Tregs) represent a promising target for inducing immune tolerance in LT, with the potential to reduce or eliminate the need for life-long immunosuppression. This review summarizes current knowledge on the roles of Tregs in LT, highlighting their mechanisms and the impact of various immunosuppressive agents on Treg stability and function. The liver's distinct immunological microenvironment, characterized by tolerogenic antigen-presenting cells and high levels of interleukin (IL)-10 and transforming growth factor-β, positions this organ as an ideal setting for Treg-mediated tolerance. We discuss Treg dynamics in LT, their association with rejection risk, and their utility as biomarkers of transplant outcomes. Emerging strategies, including the use of low-dose calcineurin inhibitors with mammalian target of rapamycin inhibitors, adoptive Treg therapy, and low-dose IL-2, aim to enhance Treg function while providing sufficient immunosuppression. Thus, the future of LT involves precision medicine approaches that integrate Treg monitoring with tailored immunosuppressive protocols to optimize long-term outcomes for LT recipients.

Interaction between serum inflammatory cytokines and brain-derived neurotrophic factor in cognitive function among first-episode schizophrenia patients

BACKGROUND The pathogenesis of cognitive impairment in schizophrenia (SCZ) remains unclear. Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor (BDNF) levels play a crucial role in the psychopathology of SCZ. However, their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated. AIM To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ. METHODS The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ (SCZ group) and 80 healthy controls (HCs group) at the Huzhou Third Municipal Hospital between August 2021 and September 2023. ELISA was employed to measure the serum levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, and BDNF. The Chinese brief cognitive test (C-BCT) and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms. RESULTS Compared to the HC group, the SCZ group exhibited elevated IL-1β and IL-6 levels, decreased BDNF levels, and reduced C-BCT scores (all P &lt; 0.001). In SCZ, BDNF was negatively correlated with IL-6 (r = -0.324, P &lt; 0.05). Information processing speed was negatively correlated with IL-6 (r = -0.315, P &lt; 0.05) and positively with BDNF (r = 0.290, P &lt; 0.05); attention, working memory, comprehensive ability, and executive function were negatively correlated with IL-1β and IL-6 (all P &lt; 0.05) and positively with BDNF (all P &lt; 0.05). Multiple regression analysis showed IL-6 influenced C-BCT dimensions (β = -0.218 to -0.327, all P &lt; 0.05); attention and executive ability were influenced by IL-1β (β = -0.199 to -0.261, all P &lt; 0.05) ; comprehensive executive ability was influenced by BDNF (β = 0.209, P &lt; 0.05) . CONCLUSION Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.

Updated genetic background of generalized pustular psoriasis as an autoinflammatory keratinization disease.

Generalized pustular psoriasis (GPP) is a severe autoinflammatory keratinization disease (AiKD) characterized by acute flares of widespread sterile pustules and high fever. GPP is potentially life-threatening. Recently clarified genetic predisposing factors for GPP suggest that the excessive activation of innate immune pathways in the skin, including of interleukin (IL)-1 and IL-36 signaling, plays a significant role in the GPP pathogenesis. IL36RN, CARD14, AP1S3, MPO, SERPINA3, BTN3A3, and MEFV have been identified as GPP-related genes. The pathogenesis of GPP provoked by variants in these seven genes is tightly associated with the excessive activation of innate immune pathways and the resulting autoinflammation in the skin. Various biologics, including inhibitors for the tumor necrosis factor, IL-17, and IL-23 pathways, are used as treatments for GPP. The new understanding of the genetic background of GPP, mentioned above, indicates that the genetic predisposing factors are predominantly related to the excessive activation of innate immunity and autoinflammation. In this context, inhibitors of inflammatory signaling, including of the IL-1 and IL-36 pathways, have been used in clinical practice and investigated as potential future therapies.

Gingival crevicular fluid Bax, Bcl-xl, interleukin-22, and transforming growth factor beta 1 levels in stage III periodontitis.

Intrinsic apoptosis plays a critical role in immune defense and inflammation. Its dysregulation is involved in various chronic diseases. The B-cell lymphoma 2 (Bcl-2) family primarily mediates this mitochondrial pathway. This study aimed to investigate the proapoptotic Bcl-2-associated X protein (Bax) and antiapoptotic B-cell lymphoma-extra large (Bcl-xl) levels and their association with interleukin-22 (IL-22) and transforming growth factor beta 1 (TGF-β1) in the gingival crevicular fluid (GCF) of patients with periodontitis. A total of 75 systemically healthy nonsmokers were enrolled, of whom 23 had stage III periodontitis, 26 had gingivitis, and 26 were periodontally healthy. Whole-mouth clinical periodontal measurements were recorded. Bax, Bcl-xl, IL-22, and TGF-β1 levels in the GCF were determined by enzyme-linked immunosorbent assay (ELISA). Data were analyzed using nonparametric statistical tests. The periodontitis group had significantly lower GCF Bax levels than the gingivitis group (p<0.05). The periodontitis and gingivitis groups had higher GCF Bcl-xl levels than the periodontally healthy group (p<0.05). GCF IL-22 levels were similar in all groups (p>0.05). The periodontitis group had lower GCF TGF-β1 levels than the gingivitis and periodontally healthy groups (p<0.05). The diseased groups had a lower GCF Bax/Bcl-xl ratio than the healthy controls (p<0.05). IL-22 was positively correlated with Bax (p<0.05). This is the first study investigating GCF Bax and Bcl-xl levels in periodontal health and disease. Increased GCF Bcl-xl levels and a decreased Bax/Bcl-xl ratio in stage III periodontitis implicate that those apoptotic proteins may be involved in the pathogenesis of periodontal disease. Further studies are needed to enlighten the possible role of Bax and Bcl-xl and their association with IL-22 and TGF-β1 in periodontal diseases. A type of cell death called intrinsic apoptosis plays an important role in the body's defense system, and its dysregulation is linked to different human diseases. The B-cell lymphoma 2-associated X protein (Bax) and B-cell lymphoma-extra large (Bcl-xl) are apoptosis-related proteins, which promote and inhibit cell death, respectively. This study aimed to investigate Bax and Bcl-xl levels and their association with the signaling proteins interleukin-22 (IL-22) and transforming growth factor beta 1 (TGF-β1) in the gingival crevicular fluid (GCF), which accumulates around the necks of the teeth of patients suffering from gum diseases such as gingivitis and periodontitis. Clinical parameters were recorded and GCF was collected. Bax, Bcl-xl, IL-22, and TGF-β1 levels were measured by biochemical assay in periodontally healthy individuals who had healthy gums (n=26) and patients with periodontitis (n=23) and gingivitis (n=26). Periodontitis patients had lower Bax levels than gingivitis patients. Periodontitis and gingivitis patients had higher Bcl-xl levels and a lower Bax/Bcl-xl ratio than periodontally healthy individuals. IL-22 was positively correlated with Bax. The present findings suggest that the apoptotic regulatory molecules may be involved in the development of gum diseases, highlighting the need for further research in this area.

The potential utility of synovial C-reactive protein, interleukin-6, and presepsin in diagnostics of periprosthetic joint infection

Background. Diagnostics of infectious complications in joint replacement surgery remains a significant challenge, particularly when microbiological analysis of biological material fails to reveal pathogen growth. The aim of the study was to determine threshold values for C-reactive protein, interleukin-6, and presepsin levels, and to assess their diagnostic value in detecting periprosthetic joint infection. Methods. A prospective cohort single-center blinded study was conducted involving cases of revision arthroplasty for periprosthetic joint infection (PJI) and aseptic prosthetic loosening. The study included 66 patients divided into two groups: Group I (n = 17), with confirmed PJI using the 2018 ICM criteria, and Group II (n = 49), with aseptic prosthetic loosening. Synovial fluid samples were subjected to bacteriological and cytological analysis, measuring levels of C-reactive protein (CRP), presepsin, and interleukin-6 (IL-6). ROC analysis, sensitivity, specificity, accuracy, and threshold values were determined for laboratory data. Results. The highest diagnostic accuracy in distinguishing between PJI and aseptic loosening was observed in the leukocyte count in synovial fluid (AUC 0.928; 95% CI: 0.837-0.977, p0.0001). Elevated synovial CRP levels were associated with infection, with an AUC of 0.776 (95% CI: 0.656-0.870, p = 0.0004), and IL-6 had an AUC of 0.712 (95% CI: 0.583-0.820; p = 0.0048). Presepsin levels, however, showed no significant difference between groups (AUC 0.582; 95% CI: 0.453-0.703; p = 0.3344). Threshold values were set at 5.6 mg/l for CRP, 1212.0 pg/ml for presepsin, and 988.5 pg/ml for IL-6. Sensitivity, specificity, and accuracy for PJI diagnosis were determined for CRP at 62.5%, 85.7%, and 80.0%; for IL-6 at 87.5%, 63.0%, and 69.4%; and for presepsin at 43.8%, 79.6%, and 70.8%, respectively. Conclusion. In cases where synovial leukocyte counts are at borderline levels, the additional assessment of synovial fluid cellular composition and simple, cost-effective markers such as synovial CRP and IL-6 may be recommended to confirm PJI.

An antibiotic that mediates immune destruction of senescent cancer cells

Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells. These effects can be replicated by salinomycin, a cation ionophore antibiotic. Salinomycin prompts a pyroptosis-apoptosis-necroptosis (PAN)optosis-like cell death in senescent cells, including apoptosis and two forms of immunogenic cell death: necroptosis and pyroptosis. Notably, we observed that salinomycin treatment or SLC25A23 suppression elevates reactive oxygen species, upregulating death receptor 5 via Jun N-terminal protein kinase (JNK) pathway activation. We show that a combination of a death receptor 5 (DR5) agonistic antibody and salinomycin is a robust senolytic cocktail. We provide evidence that this drug combination provokes a potent natural killer (NK) and CD8+ T cell-mediated immune destruction of senescent cancer cells, mediated by the pyroptotic cytokine interleukin 18 (IL18).

The Role of the cGAS/STING Pathway in Arsenic-Induced Neurotoxicity: Insights from the Crosstalk Between Astrocytes and Neurons.

Arsenic is a detrimental environmental toxicant linked to neurological damage; however, the mechanisms involved remain incompletely understood. Chronic proinflammatory responses are thought to play a central role in arsenic-induced neurotoxicity. Astrocytes, which are the predominant glial cells in the central nervous system (CNS), release significant amounts of proinflammatory cytokines upon overactivation. However, the molecular mechanisms driving this response remain to be elucidated. This study aimed to elucidate the mechanisms underlying arsenic-induced astrocyte activation and the subsequent neuronal damage, both in vivo and in vitro. In a rat model of arsenic exposure, significant neuropathological damage was detected in the CA3 region of the hippocampus. Specifically, markers of astrocyte activation, such as glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS), as well as the inflammatory cytokine interleukin (IL)-1β, were significantly upregulated, and apoptosis was markedly increased, indicating neurotoxic damage. Furthermore, in vitro experiments revealed that arsenic exposure induced substantial upregulation of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), GFAP, iNOS, and IL-1β in astrocytes, accompanied by an increase in IL-1β secretion into the culture supernatant. In addition, co-culturing neurons with conditioned medium from arsenic-exposed astrocytes resulted in significant neuronal apoptosis. Importantly, the cGAS-STING pathway inhibitor H-151 effectively suppressed the arsenic-induced astrocyte activation and IL-1β secretion, while also reducing neuronal apoptosis in the conditioned medium. Collectively, these results indicate that arsenic exposure activates the cGAS-STING signaling pathway in astrocytes, enhancing proinflammatory activation and IL-1β expression, which in turn mediates neuronal apoptosis, representing a critical mechanism underlying arsenic-induced neurotoxicity.

Inhibition of fibulin-3 ameliorates periodontal inflammation through reducing M1 macrophage polarization via EGFR/PI3K/AKT pathway.

This study aimed to evaluate the role of fibulin-3 (FBLN3) in macrophage polarization, its mechanism, and its effect on periodontitis. We conducted studies on periodontitis using both clinical samples and ligature-induced mouse periodontitis model. The inflammatory state was assessed using microcomputed tomography, hematoxylin and eosin staining, immunohistochemical staining, and immunofluorescence staining. In vitro, bone marrow-derived macrophages, and RAW 264.7 macrophages were treated with lipopolysaccharide (LPS) and interleukin (IL)-4 to induce polarization. The role of FBLN3 in macrophage polarization was investigated using overexpression plasmids or siRNAs. Furthermore, local injection of adeno-associated virus was employed to suppress FBLN3 expression in periodontal tissues. FBLN3 levels were greater in periodontitis tissues. FBLN3 promoted M1 polarization and suppressed M2 polarization in macrophages. The overexpression of FBLN3 promoted M1 polarization via the EGFR/PI3K/AKT signaling pathway, an effect that the epidermal growth factor receptor (EGFR) inhibitor PD153035 reversed. Suppressing FBLN3 expression improved periodontal inflammation and reduced alveolar bone loss in periodontitis. FBLN3 suppression can mitigate periodontitis by decreasing the M1 macrophage ratio. FBLN3 regulates M1 macrophage polarization through the EGFR/PI3K/AKT signaling pathway. Disruption in the collaboration between extracellular matrix (ECM) and immune system is a significant pathology in periodontitis. Macrophages are a crucial part of the immune system and have unique functions, such as polarization. Fibulin-3, an ECM protein, may play a vital role in this dynamic interplay. Fibulin-3 expression is elevated in periodontitis and is closely related to immune cell function. Inhibiting fibulin-3 can alleviate periodontitis by reducing infiltration of immune cells and M1 macrophage ratio. Furthermore, fibulin-3 promoted macrophage M1 polarization by activating the PI3K/AKT signaling pathway through EGFR binding. Our findings offer a clinically relevant rationale for immune response modulation through fibulin-3.

Alkali burn injury model of meibomian gland dysfunction in mice.

To establish a stable, short-time, low-cost and reliable murine model of meibomian gland dysfunction (MGD). A filter paper sheet soaked in 1.0 mol/L sodium hydroxide (NaOH) solution was used to touch the eyelid margin of C57BL/6J mice for 10s to establish the model. The other eye was left untreated as a control group. Eyelid margin morphological changes and the meibomian glands (MGs) were observed by slit lamp microscopy on days 5 and 10 post-burn. Hematoxylin-eosin (HE) staining and Oil red O staining were adopted in detecting the changes in MGs morphology and lipid deposition. Real-time polymerase chain reaction, Western blot, immunofluorescence staining and immunohistochemical staining were used to detect interleukin (IL)-6, IL-1β, IL-18, tumor necroses factor (TNF)-α, interferon (IFN)-γ, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), 3-nitroturosine (3-NT), 4-hydroxynonenal (4-HNE) and cytokeratin 10 (K10) expression changes in MGs. MGs showed plugging of orifice, glandular deficiency, abnormal acinar morphology, ductal dilatation, and lipid deposition after alkali burn. The expressions of IL-6, IL-18, IL-1β, IFN-γ, and TNF-α indicators of inflammation and oxidative stress in MGs tissues were significantly increased. Abnormal keratinization increased in the MG duct. A murine model of MGD is established by alkali burn of the eyelid margin that matches the clinical presentation of MGD providing a stable, short-time, low-cost, and reliable MGD model. The new method suggests efficient avenues for future research.

Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model

IntroductionSublingual immunotherapy (SLIT) is an effective and injection-free route for allergen-specific immunotherapy (AIT). Mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo) has been identified as a novel delivery platform with immunomodulatory capacities. In addition, targeting agents such as aptamers (Apt) have been extensively used for specific delivery approaches such as direct delivery of allergen formulations to dendritic cells (DC) to improve the efficacy of specific immunotherapy. In this study, we assessed the effects of MSC-derived Exos containing ovalbumin (Ova) which decorated with DC-specific aptamer in allergic rhinitis mice model.Materials and methodsExos were harvested from adipose tissue-derived MSCs, and Exo-Apt-Ova complex was formulated. Then, Ova-induced allergic asthma model was simulated and sensitized BALB/c mice were treated sublingually with Exo-Apt-Ova complex (5 µg Ova) twice weekly for 8 weeks. Ova-specific IgE levels in serum and concentrations of interferon-gamma (IFN-γ), interleukin (IL)-4, and transforming growth factor-beta (TGF-β) in the supernatant of cultured splenocytes were evaluated using enzyme-linked immunosorbent assay (ELISA). In addition, lung histologic analysis and nasopharyngeal lavage fluid (NALF) cell count were performed.ResultsAdministration of Ova-incorporated Apt-modified Exos dramatically increased IFN-γ and TGF-β levels, and decreased IL-4 and IgE levels. In addition, inflammatory responses in the lung tissue and the number of eosinophils in NALF decreased.ConclusionSLIT using Exo-Ova (5 µg) decorated with DC-specific aptamer induced immunomodulatory responses and remarkably attenuated allergic airway inflammation in mice.

Discordance Between Triglycerides, Remnant Cholesterol and Systemic Inflammation in Patients with Schizophrenia

Background/Objectives: Hypertriglyceridaemia and systemic inflammation are prevalent in patients with schizophrenia and contribute to an increased risk of cardiovascular disease. Although elevated triglycerides (TGs) and remnant cholesterol are linked to inflammation in the general population and individuals with metabolic syndrome, whether they are associated in patients with schizophrenia remains unclear. Methods: Fasting levels of TG, cholesterol (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and remnant cholesterol)), and markers of systemic inflammation including high-sensitivity C-reactive protein (hsCRP), leukocyte counts and their differentials (neutrophils, monocytes and lymphocytes) were determined in 147 patients diagnosed with schizophrenia on long-term antipsychotic regimens and compared with 56 age- and sex-matched healthy controls. Apolipoprotein B and glycosylation of acute phase reactant (GlycA) signatures were assessed by NMR. Circulating cytokine levels were measured by a cytokine/chemokine multiplex assay. Results: Patients with schizophrenia had markedly elevated TG and remnant cholesterol relative to controls and had evidence of systemic inflammation with increased circulating hsCRP, GlycA, leukocyte, neutrophil counts and neutrophil-to-lymphocyte ratio (NLR). Unexpectedly TG and remnant cholesterol did not correlate with systemic inflammatory markers in patients with schizophrenia, and differences in inflammatory markers between controls and patients persisted after adjusting for the lipid profile. Interleukin (IL)-10 levels were increased in patients with schizophrenia, suggesting an anti-inflammatory signature. Conclusions: The discordance between TG, remnant cholesterol and systemic inflammation in patients with schizophrenia suggests these are likely independent contributors to cardiovascular risk in this population.

The extracellular CIRP as a predictive marker for the endothelial dysfunction in chronic obstructive pulmonary disease combined with pulmonary hypertension

BackgroundPulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD), distinguished by pulmonary endothelial dysfunction. The extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern (DAMP) that triggers inflammation and causes vascular endothelial dysfunction in COPD-PH.MethodsThe expression levels of CIRP were compared in peripheral lung tissues among 40 individuals. Moreover, A prospective analysis was conducted on serum levels of eCIRP, interleukin (IL) 1β, IL-33, endothelin-1 (ET-1), and nitric oxide (NO) in 150 COPD patients and 50 healthy control individuals at Jiangsu Taizhou Peoples Hospital. The study aimed to compare these serum levels and correlations among COPD-PH group, COPD non-PH group and the normal group.ResultsWe found higher CIRP levels in COPD-PH compared to COPD non-PH and the normal in lung tissue samples. A prospective analysis showed higher serum levels of eCIRP, IL-1β, IL-33, and ET 1 in COPD-PH, while a noticeable reduction in NO levels. There exists a correlation between the severity of COPD-PH and elevated levels of eCIRP, proinflammatory cytokines like IL-1β and IL-33, along with indicators of endothelial dysfunction like endothelin-1 ET-1 and NO. Moreover, the serum eCIRP level demonstrated a notable positive correlation with the levels of IL-1β, IL-33, PCT, and ET-1, while displaying a negative correlation with NO and Peripheral Oxygen Saturation (SpO2). Moreover, the serum eCIRP level demonstrated a notable positive correlation with the levels of IL-1β, IL-33, PCT, and ET-1, while displaying a negative correlation with NO and SpO2. Moreover, an assessment of independent risk factors for COPD-PH with ROC curve analysis, gauged the predictive value of serum eCIRP, IL-1β, IL-33, ET-1, and NO levels in diagnosing COPD-PH. Elevated eCIRP, IL-33, and ET-1 levels significantly correlated with COPD-PH, highlighting eCIRP’s strong predictive value for this condition.ConclusioneCIRP levels could serve as a valuable biomarker for predicting endothelial dysfunction in COPD-PH.

Paracentrotus lividus sea urchin gonadal extract mitigates neurotoxicity and inflammatory signaling in a rat model of Parkinson's disease.

The present study investigates the neuroprotective effects of the sea urchin Paracentrotus lividus gonadal extract on rotenone-induced neurotoxicity in a Parkinson's disease (PD) rat model. Parkinson's disease, characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN), is exacerbated by oxidative stress and neuroinflammation. The study involved fifty Wistar rats divided into five groups: control, dimethyl sulfoxide (DMSO) control, Paracentrotus lividus gonadal extract-treated, rotenone-treated, and combined rotenone with Paracentrotus lividus gonadal extract-treated. Behavioral assessments included the rotarod and open field tests, while biochemical analyses measured oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH)), antioxidants (superoxide dismutase (SOD), catalase (CAT)), pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), and neurotransmitters (dopamine (DA), levodopa (L-Dopa)). Histological and immunohistochemical analyses evaluated the neuronal integrity and tyrosine hydroxylase (TH) and alpha-synuclein expression. The results showed that Paracentrotus lividus gonadal extract significantly mitigated rotenone-induced motor deficits and improved locomotor activity. Biochemically, the extract reduced oxidative stress and inflammation markers while enhancing antioxidant levels. Histologically, it restored neuronal integrity and reduced alpha-synuclein accumulation. Molecularly, it increased tyrosine hydroxylase and dopa decarboxylase gene expression, essential for dopamine synthesis. These findings suggest that Paracentrotus lividus gonadal extract exerts neuroprotective effects by modulating oxidative stress, neuroinflammation, and dopaminergic neuron integrity, highlighting its potential as a therapeutic agent for Parkinson's disease.

Developmental patterns of intestinal group 3 innate lymphoid cells in piglets and their response to enterotoxigenic Escherichia coli infection

Diarrhoea and preweaning mortality in piglets are crucial factors impacting the economic sustainability of the swine industry. Pathogenic infections are among the main causes of diarrhea and mortality. Group 3 innate lymphoid cells (ILC3s) are crucial for safeguarding against pathogenic infections. However, knowledge regarding the development and function of ILC3s in suckling piglets is currently limited. Our findings demonstrate that the development of ILC3s in suckling piglets gradually progresses from day 1 to day 21, with a notable increase observed on day 28. Additionally, the development of NKp46+ILC3s and the production of interleukin (IL)-17A by ILC3s displayed consistent patterns with the changes observed in ILC3s. Notably, interferon (IFN)-γ levels significantly increased on day 14. Moreover, the production of IFN-γ by NKp46+ILC3s was greater than that by NKp46−ILC3s. Importantly, when piglets were subjected to a 4-h challenge with enterotoxigenic Escherichia coli, both the percentages of ILC3s significantly increased, accompanied by increased IL-22 production, highlighting their importance in maintaining intestinal health. The outcomes of this study provide valuable insights for future related research.

Interleukin-22 promotes endometrial carcinoma cell proliferation and cycle progression via ERK1/2 and p38 activation.

Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors, but its underlying pathogenic mechanisms are largely obscure. Interleukin-22 (IL-22), one cytokine in the tumor immune microenvironment, was reported to be associated with carcinoma progression. Here, we aimed to investigate the regulation of IL-22 in endometrial carcinoma. Enzyme-linked immunosorbent assay (ELISA) analysis of IL-22 was done in 27 controls and 51 patients with EC. We examined the proliferative potential, cycle progression, and signaling pathways modulated by IL-22 in EC cells. Western blot analysis was performed to investigate the expression of proliferative and cycle-related proteins in EC cells. The effect of IL-22 mediated by interleukin-22 receptor alpha 1 (IL-22RA1) was examined using cell transfection with small interfering RNA (siRNA). In addition, a xenograft tumor model was performed to assess the effect of IL-22 in vivo. We demonstrated significant up-regulation of serum IL-22 concentrations in EC patients (42.59 ± 23.72pg/mL) compared to the control group (27.47 ± 8.29pg/mL). High levels of IL-22 concentrations appear to correlate with malignant clinicopathological features of EC. Treatment with IL-22 promoted cell proliferation and G1/S phase progression in Ishikawa and HEC-1B cells. Western blot analysis revealed that c-Myc, cyclin E1, cyclin-dependent kinase (CDK)2, cyclin D1, CDK4, CDK6, p-extracellular signal-regulated kinase1/2 (p-ERK1/2), and p-p38 were highly expressed in EC cells exposed to IL-22. Moreover, in the EC mice model, we found that giving exogenous IL-22 increased tumor volume and weight. Immunohistochemistry showed that intra-tumor Ki-67 expression was up-regulated upon IL-22 treatment. The IL-22-mediated changes in cell proliferation, cycle progression, and protein expression can be effectively inhibited by the ERK1/2 inhibitor U0126 and the p38 inhibitor SB202190. In addition, the role of IL-22 in EC is receptor-dependent. Our findings suggest that IL-22 promotes endometrial carcinoma cell proliferation and G1/S phase progression by activating ERK1/2 and p38 signaling. Therefore, IL-22 may represent a potential therapeutic target for the treatment of endometrial carcinoma.

Aspirin-triggered resolvin D1 modulates pulmonary and neurological inflammation in an IL-22 knock-out organic dust exposure mouse model

Agriculture dust contains many organic immunogenic compounds, and organic dust exposure is strongly associated with the development of immune-mediated chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD). Chronic organic dust exposure from agriculture sources induces chronic lung inflammatory diseases and organic dust exposure has recently been linked to an increased risk of developing dementia. The cytokine interleukin-22 (IL-22) has been established as an important mediator in the resolution and repair of lung tissues. The omega-3 fatty acid metabolite aspirin-triggered Resolvin D1 (AT-RvD1) has shown efficacy in modulating the immune response in both pulmonary and neurological inflammation but has not been explored as a therapeutic in organic dust exposure-induced neuroinflammation. Investigating the link between IL-22 and AT-RvD1 may help in developing effective therapies for these immune-mediated diseases. We aimed to investigate the link between organic dust exposure and neuroinflammation, the role of IL-22 in the pulmonary and neurological immune response to organic dust exposure, and the immune-modulating therapeutic applications of AT-RvD1 in an IL-22 knock-out mouse model of organic dust exposure. C57BL/6J (WT) and IL-22 knock-out (KO) mice were repetitively exposed to aqueous agriculture organic dust extract (DE) 5 days per week for 3 weeks (15 total instillations) and treated with AT-RvD1 either once per week (3 total injections) or 5 times per week (15 total injections) for 3 weeks and allowed to recover for 3 days. We observed a significant pulmonary and neurological immune response to DE characterized by the development of inducible bronchus associated lymphoid tissue in the lung and gliosis in the frontal areas of the brain. We also observed that IL-22 knock-out increased pulmonary and neurological inflammation severity. Animals exposed to DE and treated with AT-RvD1 displayed reduced lung pathology severity and gliosis. Our data demonstrate that DE exposure contributes to neurological inflammation and that IL-22 is crucial to effective tissue repair processes. Our data further suggest that AT-RvD1 may have potential as a novel therapeutic for organic dust exposure-induced, immune-mediated pulmonary and neurological inflammation, improving outcomes of those with these diseases.

Elevated visfatin levels illuminate the inflammatory path in bronchopulmonary dysplasia

Background. Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants caused by an imbalance between lung injury and lung repair in the developing immature lungs of the newborn. Pulmonary inflammation is an important feature in the pathogenesis of BPD. The aim of this study was to evaluate the relationship between the inflammatory microenvironment and the levels of visfatin and nesfatin-1, which are among the new adipocytokines, in BPD patients. Methods. The groups consisted of 30 patients with BPD and 30 healthy children. Plasma levels of visfatin and nesfatin-1 and inflammation-related markers including interleukin-4 (IL-4), interleukin-10 (IL-10), nuclear factor kappa B (Nf-κB) and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay (ELISA). RT-PCR was performed to evaluate the change in mRNA expression of visfatin and nesfatin-1 in the groups. Results. Visfatin levels were significantly higher in the BPD group compared to the healthy control (7.05±4.07 ng/ml vs. 2.13±1.66 ng/ml, p&lt;0.0001). There was a 1.36±0.12 fold increase in visfatin mRNA expression (p&lt;0.05) in the BPD group. There was no significant difference in plasma levels of nesfatin-1, IL-4, and IL-10 between the groups. Although MMP-9 and Nf-κB levels were significantly higher in the BPD group (p&lt;0.0001), there was no correlation between visfatin levels and MMP-9 and Nf-κB levels in BPD patients. Conclusions. This study showed that significant changes in visfatin levels in BPD patients might be associated with the risk of developing inflammation in BPD.