Thymic Stromal Lymphopoietin Levels Research Articles

Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model.

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Evaluation of Yukmijihwang-Tang as a Novel Preventive Agent in Ovalbumin-Induced Murine Asthma

Yukmijihwang-tang (YJT) is a blend of six herbal ingredients that has long been used in Asia for various diseases, including diabetes mellitus and mental decline. Here, we assessed the prophylactic efficacy of YJT in a murine model of asthma induced by ovalbumin (OVA). Male C57BL/6 mice underwent sensitization followed by an airway challenge with OVA for 1 h. YJT (100 or 300 mg/kg once daily) was administered orally for 6 days. Our analyses revealed that YJT significantly reduced inflammatory cell counts in bronchoalveolar lavage fluid (BALF), decreased the concentrations of interleukin (IL)-4, IL-5, and IL-13 in BALF, and lowered the relative mRNA levels of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor α (TNFα) in lung tissues. Histological analyses showed that YJT substantially decreased inflammation and mucus hypersecretion in the bronchial airway. YJT also effectively reduced oxidative stress, as evidenced by improved levels of malondialdehyde (MDA), total glutathione, glutathione reductase (GR), and reduced glutathione (GSH). YJT also markedly suppressed the phosphorylation of nuclear factor-kappa B (NF-κB) in lung tissues. Together, these results show that YJT effectively inhibits respiratory inflammation, mucus hypersecretion, and oxidative stress induced by OVA, suggesting its potential for asthma treatment.

Unraveling genetic threads: Identifying novel therapeutic targets for allergic rhinitis through Mendelian randomization

BackgroundAllergic rhinitis (AR) is a pervasive global health issue, and currently, there is a scarcity of targeted drug therapies available. This study aims to identify potential druggable target genes for AR using Mendelian randomization (MR) analysis. MethodsMR analysis was conducted to assess the causal effect of expression quantitative trait loci (eQTL) in the blood on AR. Data on AR were collected from 2 datasets: FinnGen(R9) (11,009 cases and 359,149 controls) and UK Biobank (25,486 cases and 87,097 controls). Colocalization analysis was utilized to assess the common causal genetic variations between the identified drug target genes and AR. We also employed available genome-wide association studies (GWAS) data to gauge the impact of druggable genes on AR biomarkers and other allergic diseases. ResultsThis study employs MR to analyze the relationship between 3410 druggable genes and AR. After Bonferroni correction, 10 genes were found to be significantly associated with AR risk (P < 0.05/3410). Colocalization analysis revealed a significant causal relationship between the expression variation of CFL1 and EFEMP2 genes and AR, sharing direct causal variants (colocalization probability PP.H3 + PP.H4 > 0.8), highlighting their importance as potential therapeutic targets for AR. The CFL1 gene showed a causal link with levels of thymic stromal lymphopoietin (TSLP), eosinophil count, and interleukin-13 (IL-13) (P = 0.016, 7.45E-16, 0.00091, respectively). EFEMP2 was also causally related to eosinophil count, IL-13, and interleukin-17 (IL-17) (P = 0.00012, 0.00091, 0.032, respectively). PheWAS analysis revealed significant associations of CFL1 with asthma, whereas EFEMP2 showed associations with both asthma and eczema. Protein-Protein Interaction (PPI) network analysis further unveiled the direct interactions of EFEMP2 and CFL1 with proteins related to immune regulation and inflammatory responses, with 77.64% of the network consisting of direct bindings, indicating their key roles in modulating AR-related immune and inflammatory responses. Notably, there was an 8.01% significant correlation between immune-related pathways and genes involved in inflammatory responses. ConclusionThese genes present notable associations with AR biomarkers and other autoimmune diseases, offering valuable targets for developing new AR therapies.

Thymic stromal lymphopoietin and digital microvascular damage in systemic sclerosis patients: A pilot study

BackgroundSystemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs. Methods75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI). ResultsThe median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), p < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), p < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels. ConclusionTSLP might have a key role in digital microvascular damage of SSc patients.

Upper Airway Alarmin Cytokine Expression in Asthma of Different Severities.

Background: The secretion of alarmin cytokines by epithelial cells, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, initiates inflammatory cascades in asthma. However, alarmin cytokine expression in the upper airways in asthma remains largely unknown. Methods: We recruited 40 participants with asthma into four groups as per the Global Initiative for Asthma (GINA) steps (10 in each group of GINA 1/2, 3, 4, and 5). Cells were derived from nasal, buccal, and throat brushings. Intracellular cytokine expression (TSLP, IL-25, and IL-33) was assessed by flow cytometry in cytokeratin 8+ (Ck8+) epithelial cells immediately following collection. Results: TSLP was significantly increased (p < 0.001) in GINA 5 patients across nasal, buccal, and throat Ck8+ epithelial cells, while IL-25 was elevated in nasal and throat samples (p < 0.003), and IL-33 levels were variable, compared with GINA 1-4 patients. Individual GINA subgroup comparison showed that TSLP levels in nasal samples from GINA 5 patients were significantly (p = 0.03) elevated but did not differ between patients with and without nasal comorbidities. IL-25 and IL-33 (obtained from nasal, buccal, and throat samples) were not significantly different in individual groups. Conclusions: Our study demonstrates for the first time that Ck8+ nasal epithelial cells from GINA 5 asthma patients express elevated levels of TSLP.

Exploring TSLP and IL-33 Serum Levels and Genetic Variants: Unveiling Their Limited Potential as Biomarkers for Mild Asthma in Children.

As the burden of mild asthma is not well understood, the significance of expanding research in the group of patients with mild asthma is emphasized. Thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33) are involved in the pathogenesis of atopy and the immune response to inhaled environmental insults, such as allergens, in asthmatic patients. Objectives: The objective of this study was to explore the correlation between specific polymorphisms within the genes encoding TSLP and IL-33, as well as the concentrations of TSLP and IL-33 in the serum, and the occurrence of pediatric mild asthma. Methods: The analysis encompassed 52 pediatric patients diagnosed with mild bronchial asthma, including both atopic and non-atopic cases, and a control group of 26 non-asthmatic children. Recruitment was conducted through a comprehensive questionnaire. Parameters such as allergic sensitization, serum levels of circulating TSLP and IL-33, and the identification of single-nucleotide polymorphisms in TSLP (rs11466750 and rs2289277) and IL-33 (rs992969 and rs1888909) were assessed for all participants. Results: Significantly lower mean serum TSLP concentrations were observed in asthmatic subjects compared to the control group, with atopic asthma patients showing even lower TSLP levels than non-atopic counterparts. No significant differences were found in mean serum IL-33 concentrations between the two groups. Considering the allele model, for both tested SNPs of IL-33, we observed that patients with asthma, atopic asthma, and atopy statistically less frequently possess the risk allele. Conclusions: Our study findings suggest that IL-33 and TSLP do not serve as ideal biomarkers for mild asthma in children. Their effectiveness as biomarkers might be more relevant for assessing disease severity rather than identifying asthma in pediatric patients. Further research focusing on the association between TSLP and IL-33 gene polymorphisms and asthma is expected to significantly advance disease management.

A Comparative Study on Serum Levels of “Thymic Stromal Lymphopoietin” Between Patients with Psoriasis Vulgaris and Healthy Individuals: A Case-Control Study

Abstract Background: Thymic stromal lymphopoietin (TSLP) is a cytokine initially implicated to be associated with allergic disorders inducing Th2 response. Emerging studies have shown that TSLP is also involved in autoimmune diseases. In psoriasis, TSLP acts in synergy with T cell-derived CD40L to promote the release of IL-23 from dendritic cells. IL-23 is responsible for the inappropriate immune reaction and keratinocyte proliferation in psoriasis. Targeting TSLP could be a novel therapeutic approach in the treatment of psoriasis. Objective: To compare the serum levels of TSLP between patients with psoriasis and healthy individuals. Materials and Methods: A prospective hospital-based case-control study was carried out on 38 patients with psoriasis. The severity of psoriasis was graded into mild, moderate, and severe according to PASI. A total of 30 healthy individuals with matched age and sex were taken as controls. 5 ml of venous blood was collected, centrifuged, and the collected serum was stored at -80°C until quantitative assessment by sandwich enzyme-linked immunosorbent assay (ELISA) technique. Results: TSLP has been found to be significantly elevated in the sera of cases (0.1380178 pg/ml) than in controls (0.1125974 pg/ml). There was also a significant proportionate increase in the mean TSLP with the mean PASI score. Limitations: The sample size was small and we could not follow-up the cases to study the changes in TSLP levels with remission of the lesions. Conclusion: We found that serum TSLP was elevated in psoriasis patients and correlated with disease severity, indicating a possible pathogenetic role.

The role of thymic stromal lymphopoietin in cutaneous disorders.

Thymic Stromal Lymphopoietin (TSLP) is an important cytokine that invokes early immune responses. TSLP, an IL-7-like cytokine encoded by the TSLP gene, activates JAK1 and JAK2 signaling pathways, stimulating dendritic cells to induce inflammatory Th2 cells. This cytokine is associated with pruritus in various cutaneous disorders, particularly atopic dermatitis. Varying levels of the cytokine TSLP have been demonstrated in studies of different cutaneous disorders. Pharmacological treatment targeting TSLP has been explored recently, particularly in the realm of atopic dermatitis.This review explores the relation of TSLP to cutaneous diseases, highlighting its potential as a biomarker for monitoring disease progression in discoid lupus erythematosus (DLE). The pharmacological therapy involving TSLP is discussed, along with the potential role of TSLP promotion in the treatment of alopecia areata. This overview examines the background, structure, and functions of TSLP, with a focus on its association with cutaneous disorders and a special focus on the impact of the atopic march.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

Resveratrol modulates the Nrf2/NF-κB pathway and inhibits TSLP-mediated atopic march.

Resveratrol has been found to have anti-inflammatory and anti-allergic properties. The effects of resveratrol on thymic stromal lymphopoietin (TSLP)-mediated atopic march remain unclear. To explore the potential role of resveratrol in TSLP-mediated atopic march. The atopic march mouse model was established by topical application of MC903 (a vitamin D3 analog). Following the treatment with resveratrol, airway resistance in mice was discovered by pulmonary function apparatus, and the number of total cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid was counted. The histopathological features of pulmonary and ear skin tissues, inflammation, and cell infiltration were determined by hematoxylin and eosin staining. The messenger RNA (mRNA) levels of TSLP, immunoglobulin E, interleukin (IL)-4, IL-5, and IL-13 were measured by real-time quantitative polymerase chain reaction. The protein expression of nuclear factor kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling-associated molecules (p-p65, p65, p-I kappa B kinase alpha (IκBα), IκBα, Nrf2, and TSLP) in lung and ear skin tissues were assessed by Western blot analysis. Resveratrol attenuated airway resistance and infiltration of total cells, eosinophils, and neutrophils in both lung and ear skin tissues. Resveratrol ameliorates serum inflammatory markers in allergic mice. Moreover, the phosphorylation levels of NF-κB pathway-related proteins were significantly reduced by administration of resveratrol in allergic lung and ear skin tissues. Similarly, the protein expression of TSLP in both lung and ear skin tissues was reduced by resveratrol, and Nrf2, a protector molecule, was increased with resveratrol treatment. Resveratrol attenuates TSLP-reduced atopic march through ameliorating inflammation and cell infiltration in pulmonary and ear skin tissues by inhibiting the abnormal activation of NF-κB signaling pathway.

Bombesin receptor-activated protein homolog deficiency altered the pattern of pathological changes of psoriasis - like skin lesion in mice.

This study investigated the potential role of the mouse homolog of bombesin receptor-activated protein (BRAP) in imiquimod (IMQ) induced psoriasis - like skin inflammation. The expression of both human BRAP, encoded by C6orf89, and its mouse homolog, encoded by BC004004, has been found to be expressed abundantly in the keratinocytes. BC004004 knockout mice (BC004004-/-) were topically treated with IMQ daily for 7 days to test whether they were more vulnerable to psoriasis - like inflammation. We found that those mice exhibited an altered pattern of inflammation process compared to isogenic wild type control mice (BC004004+/+). BC004004-/- mice developed skin lesions with earlier and more acute onset, as well as a quicker remission. The cytokines related to pathogenesis of psoriasis also exhibited different expression patterns in IMQ treated BC004004-/- mice. On day 4 of IMQ treatment, BC004004-/- mice exhibited a higher expression level of IL-17A compared to BC004004+/+ mice, suggesting a more robust activation of Th17 cells in the knockout mice. The serum level of thymic stromal lymphopoietin (TSLP), one of the keratinocyte derived cytokines, was also increased in BC004004-/- mice and reached its peak on day 4. Knockdown of BRAP in cultured human keratinocyte-derived HaCaT cells by siRNA silencing led to increased release of TSLP. Our data suggest that the elevated of level of TSLP released from keratinocytes due to BRAP deficiency might mediate the crosstalk between the epidermal cells and immune cells and thereby contributing to the altered pathological changes observed in psoriasis - like skin lesion in knockout mice.

Antibody targeting TSLP suppresses DSS-induced colitis and activation of the JAK2/STAT5 pathway in mice.

There is currently no safe or effective treatment for inflammatory bowel disease (IBD), which is defined as recurrent and persistent intestinal inflammation. Thymic stromal lymphopoietin (TSLP) has been shown to be associated with the pathogenesis of IBD, and the JAK2/STAT5 signalling pathway has demonstrated much promise as a novel therapeutic target for IBD. In this study, we first evaluated levels of TSLP in dextran sodium sulphate (DSS)-induced IBD mice. Second, we applied tezepelumab, an anti-TSLP monoclonal antibody (20μg per mouse, intraperitoneally), to DSS-induced IBD mice and quantified the signs of histopathological change, intestinal inflammation, and integrity of the mucosal barrier. In addition, the effect of DSS and/or tezepelumab on the phosphorylation of the JAK/STAT pathway was investigated. TSLP expression levels were elevated in DSS-induced IBD mice, whereas TSLP antibody treatment suppressed the pathological features associated with IBD and alleviated intestinal inflammation and mucosal barrier disruption. Moreover, level of phosphorylated JAK2/STAT5 were increased in DSS-induced IBD mice, but were strongly decreased in the presence of tezepelumab. Our findings suggest that targeting TSLP via the JAK2/STAT5 signalling pathway may be an effective approach for the treatment of IBD.

Amygdalin Improves Allergic Asthma via the Thymic Stromal Lymphopoietin–dendritic Cell–OX40 Ligand Axis in a Mouse Model

Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable treatment strategies are the focus of current research on pediatric asthma. Amygdalin, mainly present in bitter almonds, has anti-inflammatory and immunoregulatory potential, but its effect on asthma remains uninvestigated. Here, the impact of amygdalin on the thymic stromal lymphopoietin (TSLP)–dendritic cell (DC)–OX40L axis was investigated.&#x0D; A BALB/c mouse model for allergic asthma was established using the ovalbumin-sensitization method. Amygdalin treatment was administered between days 21 and 27 of the protocol. Cell numbers and hematoxylin and eosin (H&amp;E) staining in bronchoalveolar lavage fluid (BALF) were used to observe the impact of amygdalin on airway inflammation. TSLP, IL-4, IL-5, IL-13, and IFN-γ concentrations were determined via Enzyme-linked immunosorbent assay (ELISA). TSLP, GATA-3, and T-bet proteins were measured using western blotting. Cell-surface receptor expression on DCs (MHC II, CD80, and CD86) was assessed via flow cytometry. OX40L mRNA and protein levels were detected using western blotting and qRT-PCR, respectively.&#x0D; Amygdalin treatment attenuated airway inflammation decreased BALF TSLP levels, inhibited DC maturation, restrained TSLP-induced DC surface marker expression (MHCII, CD80, and CD86), and further decreased OX40L levels in activated DCs. This occurred together with decreased Th2 cytokine levels (IL-4, IL-5, and IL-13) and GATA3 expression, whereas Th1 cytokine (IFN-γ) levels and T-bet expression increased.&#x0D; Amygdalin thus regulates the Th1/Th2 balance through the TSLP–DC–OX40L axis to participate in inflammation development in the airways, providing a basis for potential allergic asthma treatments.

Association of Periodontitis and Atopic Dermatitis with the Levels of IL-13, IL-31, and TSLP in the Gingival Crevicular Fluid.

Emerging epidemiological evidence links atopic dermatitis (AD) and periodontitis, although the mechanisms remain unclear. Th2-derived cytokines are key in the development of both diseases, and different gingival crevicular fluid (GCF) profiles among healthy and diseased subjects have been previously reported. This case-control study examined the GCF levels of interleukins (IL)-13, IL-31, and thymic stromal lymphopoietin (TSLP) in 29 subjects with moderate-to-severe AD and 33 controls. All subjects underwent comprehensive clinical and oral evaluations, followed by GCF collection. GCF levels of IL-13, IL-31, and TSLP were assessed using a multiplex-bead immunoassay. Demographic and periodontal parameters were similar among groups (p > 0.05). The GCF levels of IL-31 and TSLP were higher in AD subjects compared to controls (p < 0.05), whereas no significant differences in the GCF levels of IL-13 were noticed (p = 0.377). Moderate-to-severe AD was positively associated with the GCF levels of IL-31 and TSLP, whereas severe periodontitis was negatively associated with IL-31 (p < 0.05). The GCF levels of IL-13 showed no significant associations with either condition (p = 0.689). There was no significant interaction between AD and periodontitis for IL-31 (p < 0.869). These results suggest that AD and periodontitis independently influence the GCF levels of IL-31 in opposing ways, whereas AD alone influences the levels of TSLP.

Effect of moxibustion of acupoints for both lung and intestine disorders on lung inflammation and intestinal short-chain fatty acids in asthmatic model rats

To explore the mechanism of moxibustion in the treatment of asthmatic inflammation from the point of short-chain fatty acids (SCFAs) in rats with asthma. A total of 48 SD rats (half male and half female) were randomly divided into 4 groups： normal, model, lung treatment and joint-treatment of lung and intestine (joint-treatment), with 12 rats in each group. The asthma model was made by subcutaneous (bilateral back and inguinal regions) and intraperitoneal injection of mixture solution of ovalbumin and aluminium hydroxide gel (on day 1 and 8) and followed by inhalation of atomized 1% ovalbumin (20 min from day 15, once daily for one week). Moxibustion was applied to bilateral "Feishu" (BL13) for rats of the lung treatment group or bilateral "Feishu" (BL13) and "Tianshu" (ST25) for rats of the joint treatment group. One hour after the intervention, the rats in the later three groups were separately given atomized 1% ovalbumin solution inhalation for 20 min. The treatment was conducted for 30 min, once daily for 14 consecutive days. At the end of the intervention, the percentage of inflammatory cells in blood was detected by biochemical method and histopathological changes of the lung were observed after H.E. staining. The inflammatory cells in the bronchoalveolar lavage fluid (BALF) were counted after Wright-Giemsa staining. The mRNA expressions of interleukin (IL)-4, IL-5, IL-13, IL-17, IL-33, leukotriene (LT), thymic stromal lymphopoietin (TSLP) and prostaglandin D2 (PGD2) were detected by real-time PCR, and the contents of SCFAs in rats' feces were detected by gas chromatography-mass spectrometry. Relevant to the normal group, the model group had an obvious increase in the percentages of neutrophils, lymphocytes and eosinophils in the blood, the percentages of neutrophils and eosinophils in the BALF, and in the expression levels of PGD2, TSLP, LT, IL-4, IL-5, IL-13, IL-17 and IL-33 mRNAs in the lung tissues (P<0.01, P<0.05), and a marked decrease in the contents of acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid in feces (P<0.05, P<0.01). After the treatment, the percentages of neutrophils and lymphocytes in the peripheral blood, eosinophils in the BALF, and the expression levels of PGD2, TSLP, LT, IL-4, IL-17, IL-33 mRNAs in the lung tissues in both the lung treatment and joint treatment groups, as well as neutrophils of BALF, and expression of IL-5 and IL-13 mRNAs in the joint treatment group were significantly down-regulated (P<0.01, P<0.05), while the contents of acetic acid, propionic acid and valerate in the lung treatment group, and acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid in the joint treatment group were all strikingly increased (P<0.05, P<0.01). The effect of the joint treatment was superior to that of lung treatment in down-regulating the expressions of LT and IL-5 mRNAs (P<0.05, P<0.01) and up-requlating the content of propionic acid (P<0.05). Results of H.E. staining showed thickened alveolar wall, infiltration of a large number of inflammatory cells and interstitial fibrous tissue hyperplasia around the bronchus and scattered arrangement of cells of the lung tissue in the model group, which was relatively milder in both lung treatment and joint treatment groups, particularly the later. Joint treatment of asthma from the lung and intestine can better regulate the contents of intestinal SCFAs and alleviate the inflammatory response of asthmatic model rats, thus, intestinal SCFAs may be involved in the process of moxibustion in improving inflammatory response.

Thymic stromal lymphopoietin: evaluating its role as a new marker related to presence of psoriasis vulgaris and its severity

Background Thymic stromal lymphopoietin (TSLP), a proallergic cytokine, and T cell-derived CD40 ligand (CD40L) may collaborate to increase the production of IL-23 in psoriasis patients. One key cytokine, IL-23, is responsible for the unwarranted immune response in psoriasis sufferers. Aim The current study aims to shed light on the possible role of TSLP as a novel biomarker related to presence of psoriasis vulgaris lesions and its severe forms with exclusion of people with atopic dermatitis, allergic rhinitis, rheumatoid arthritis, graft versus host disease (GVHD), blood diseases and patient on anticoagulant therapy as well as pregnant and lactating females. Patients and methods 40 subjects with psoriasis vulgaris participated in the current case-controlled research, whereas 40 healthy volunteers of similar age and gender served as the control group. The degree and extent of the illness were evaluated utilizing the psoriasis area and severity index (PASI) score. Serum was separated after blood samples from the venous blood of the subjects and control participants were taken. As soon as possible, the serum samples were frozen at −20°C. The Sandwich Enzyme-Linked Immunosorbant Assay (ELISA) was utilized to quantify serum TSLP. Results The case group’s serum TSLP levels rose statistically substantially more than those of the control group. In the cases group, there was a statistically strong positive relation between serum TSLP levels and PASI scores (P: &lt; 0.001). There is a statistically strong positive relation between serum TSLP and patients’ age and illness duration, a statistically substantial rise in blood TSLP values in psoriatic arthritis patients and smokers. Conclusion Patients with psoriasis have higher serum TSLP levels, which are proportional to the disease’s severity.

Nasal fluid sample as a reliable matrix for determination of cytokine levels in childhood asthma

Abstract Objectives Childhood asthma is a chronic disease with high incidence worldwide. As a lifelong disease, asthma has episodes. Inflammation continues to occur in the clinical remission of asthma. It can be difficult to diagnose childhood asthma, especially in clinical remission. We hypothesized that some cytokines secreted to nasal fluid from the airway during inflammation might help diagnose clinical remission of asthma. Moreover, sampling nasal fluid is an easy and non-invasive procedure, so it may be a preferable sampling method. Methods We measured levels of some interleukins (ILs), which are IL-4, IL-5, IL-6, IL-12p70, IL-13, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), periostin and thymic stromal lymphopoietin (TSLP) by Luminex magnetic bead-based immunoassay in nasal fluid and in serum of asthmatic children in clinical remission. Results We found that IL-5, IL-6, IL-33, and periostin had elevated levels in nasal fluid. IL-5 and IL-33 had increased levels in the nasal fluid of the patients with immunoglobulin E (IgE) high and low phenotypes. While the nasal fluid TSLP levels were positively correlated with most of the increased serum cytokine levels of non-allergic asthmatic children, the nasal fluid GM-CSF levels were positively correlated with most of the increased serum cytokine levels of the allergic asthmatic children. Conclusions IL-5, IL-6, IL-33, and periostin had elevated levels in the nasal fluid of the patients in clinical remission. The nasal fluid GM-CSF levels of the allergic patients and nasal fluid TSLP levels of the non-allergic patients had a positive correlation with most of the serum cytokine levels. Thus, our results showed that nasal fluid might be a preferable biological sample to diagnose asthma in children.

Association of Inflammatory Indicators and Clinical Signs and Itch in Atopic Dermatitis Patients Treated with Simiao Pill Combined with Halomethasone Cream.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by symptoms such as itchiness, scaling, and erythema. Previous studies have suggested that inflammatory indicators obtained from peripheral blood cell count can serve as markers for atopic dermatitis pruritus and severity. The objective of this study was to investigate whether these indicators are associated with treatment efficacy in AD patients who received a combination of halomethasone cream and Simiao pill (SMP). 131 adult patients diagnosed with AD between January 2020 to August 2022 and treated with topical halometasone ointment combined with oral Simiao pill for a month were recruited and clinical dates of patients were collected. Inflammatory indicators included Eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum leukotriene B4 (LTB4), and thymic stromal lymphopoietin (TSLP) and clinical indexes for assessing eczema area and severity index (EASI) and peak pruritus-numerical rating scale (PP-NRS). Relationship of baseline and changes of these Inflammatory indicators and that of clinical indexes were analyzed. ELR, NLR, LTB4, and TSLP levels have positive association with EASI before treatment, and baseline ELR and LTB4 levels have positive relationship with PP-NRS. ELR, NLR, LTB4, and TSLP showed a significant decrease at week 2 and the low levels were maintained until week 8 after treatment, while no significant changes were observed in levels of MLR and PLR. There was a significant correlation between the decrease of ELR and the decreases of EASI and PP-NRS at weeks 2, 4 and 8 of the treatment. ELR may serve as an effective and convenient indicator in assessing the disease severity and efficacy of SMP therapy for AD.

Effects of total alkaloids from Alstonia scholaris (L.) R. Br. on ovalbumin-induced asthma mice

Ethnopharmacological relevanceMore than 300 million people worldwide suffer from asthma, a chronic respiratory inflammatory disease. Total alkaloids (TA) were extracted from the ethnic medicinal plant Alstonia solaris (L.) R.Br., which is used to treat respiratory diseases. They may be effective drugs for treating asthma, but research is still needed to determine their effectiveness and mechanism in treating asthma. Aim of the studyTo further understand TA's role in the treatment of asthma and to support the phase II trial of the drug. Materials and methodsIn this study, we investigated the effects of TA in a mouse asthma model produced by Ovalbumin (OVA). H&E and PAS staining were used to observe the histopathological features of lung. airway hyperresponsiveness (AHR) was detected by ventilator; The expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and E-cadherin in the lungs was evaluated by IHC. The concentrations of Mucin5AC (MUC5AC), eotaxin, IL-4, IL-5, IL-9, IL-13, interferon (IFN)-γ, IL-6, IL-8, IL-17A, IL-33, IL-25, thymic stromal lymphopoietin (TSLP), monocyte chemoattractant protein 1 (MCP-1), leukotriene (LT) B4, LTC4, LTD4, LTE4 in bronchoalveolar lavage fluid (BALF) and total IgE (tIgE), OVA-Specific IgE (OVA-IgE) in serum were measured by ELISA. ILC2s and eosinophils were detected in lung tissue by flow cytometry. The gene expression levels of IL-33 and ST2 were detected by RT-qPCR. ResultsAdministration of TA reduced pulmonary inflammatory symptoms, MUC5AC production in the BALF, and AHR. At the same time, TA inhibited eotaxin production and eosinophil recruitment. Moreover, TA significantly decreased Th2 and Th17 cytokines and increased Th1 cytokines, contributing to restore the balance between Th1 and Th2 and Th17 cytokines. TA may reduce ILC2s numbers by inhibiting IL-33, IL-25, and TSLP levels in BALF and IL-33/ST2 signaling in lung tissue. Finally, TA decreased tIgE, OVA-IgE, and MCP-1 levels and subsequently inhibited mast cell activation and leukotriene release. ConclusionsThese findings imply that TA may be an effective immunoregulatory medication for the management and prevention of asthma.

Esculentoside A ameliorates DNCB-induced atopic dermatitis by suppressing the ROS-NLRP3 axis via activating the Nrf2 pathway.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence. Inflammation and oxidative stress are strongly associated with AD progression. Esculentoside A (EsA) inhibits inflammation and oxidative stress in various diseases. However, whether EsA mitigates AD by suppressing inflammation and oxidative stress remains unknown. A mouse model of AD was constructed by the induction of 1-chloro-2,4-dinitrochlorobenzene (DNCB). The mechanism of EsA and its effects on AD symptoms, pathology, inflammation and oxidative stress were investigated through histopathological staining, enzyme-linked immunosorbent assay, blood cells analysis, colorimetric measurement and western blot analysis. EsA improved the clinical symptoms and increased clinical skin scores in AD mice. Skin thickening of the epidermis and dermal tissues and the mast cell numbers in AD mice were reduced with the EsA treatment. EsA decreased the relative mRNA level of thymic stromal lymphopoietin, interleukin (IL)-4, IL-5 and IL-13; the serum concentrations of immunoglobulin E (IgE) and IL-6; and the numbers of white blood cells (WBC) and WBC subtypes, including basophil, lymphocytes, eosinophil, neutrophil and monocytes in DNCB-induced mice. DNCB caused higher levels of oxidative stress, which was reversed with the administration of EsA. Mechanically, EsA upregulated the expression of Nrf2 but downregulated the level of NLRP3 inflammasome in AD mice. The inhibitor of Nrf2 significantly recovered the EsA-induced changes in the NLRP3 inflammasome proteins in DNCB-treated mice. Therefore, EsA improved the clinical and pathological symptoms, inflammation and oxidative stress experienced by DNCB-induced mice and was involved in the inactivation of NLRP3 inflammasome by activating Nrf2.