Pathogenesis Of Inflammatory Diseases Research Articles

The Expression Patterns of Non-Coding RNAs in Periodontal Disease.

During the last few decades there has been a growing interest in understanding the involvement of epigenetics in the pathogenesis and treatment of periodontal disease. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), may serve as epigenetic modifiers affecting the expression of genes involved in the pathogenesis of inflammatory and autoimmune diseases. There is increasing evidence supporting the idea that the function of all three types of ncRNAs seems to be interdependent. LncRNAs can act as miRNA decoys, while circRNAs can act as miRNA sponges, leading to the re-expression of miRNA target genes. The purpose of this review is to evaluate the expression patterns of ncRNAs in periodontal disease. Studies demonstrate a positive correlation between miRNA expression and periodontitis; however, this cannot be claimed for lncRNAs and circRNAs, which appear to be differentially expressed in periodontitis patients. Several studies have also suggested utilizing ncRNAs as diagnostic and prognostic biomarkers in periodontitis, or even as potential therapeutic targets; Nevetheless, the evidence to support this is premature. Future well-designed research remains necessary to establish the functional role of ncRNAs in the evolution and progression of periodontal disease.

Urolithin A suppresses NLRP3 inflammasome activation by inhibiting the generation of reactive oxygen species and prevents monosodium urate crystal-induced peritonitis.

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the maturation of interleukin-1β (IL-1β) and is implicated in the pathogenesis of various inflammatory diseases. Urolithin A, a gut microbial metabolite of ellagic acid, reportedly exerts antiinflammatory effects in vitro and in vivo. However, whether urolithin A suppresses NLRP3 inflammasome activation is unclear. In this study, urolithin A inhibited the cleavage of NLRP3 inflammasome agonist-induced caspase-1, maturation of IL-1β, and activation of pyroptosis in lipopolysaccharide-primed mouse bone marrow-derived macrophages. Urolithin A reduced generation of intracellular and mitochondrial reactive oxygen species (ROS) and restricted the interaction between thioredoxin-interacting protein and NLRP3, which attenuated NLRP3 inflammasome activation. Urolithin A administration prevented monosodium urate-induced peritonitis in mice. Collectively, these findings indicate that urolithin A suppresses NLRP3 inflammasome activation, at least partially, by repressing the generation of intracellular and mitochondrial ROS.

The RIPK1 death domain restrains ZBP1- and TRIF-mediated cell death and inflammation

RIPK1 is a multi-functional kinase that regulates cell death and inflammation and has been implicated in the pathogenesis of inflammatory diseases. RIPK1 acts in a kinase-dependent and kinase-independent manner to promote or suppress apoptosis and necroptosis, but the underlying mechanisms remain poorly understood. Here, we show that a mutation (R588E) disrupting the RIPK1 death domain (DD) caused perinatal lethality induced by ZBP1-mediated necroptosis. Additionally, these mice developed postnatal inflammatory pathology, which was mediated by necroptosis-independent TNFR1, TRADD, and TRIF signaling, partially requiring RIPK3. Our biochemical mechanistic studies revealed that ZBP1- and TRIF-mediated activation of RIPK3 required RIPK1 kinase activity in wild-type cells but not in Ripk1R588E/R588E cells, suggesting that DD-dependent oligomerization of RIPK1 and its interaction with FADD determine the mechanisms of RIPK3 activation by ZBP1 and TRIF. Collectively, these findings revealed a critical physiological role of DD-dependent RIPK1 signaling that is important for the regulation of tissue homeostasis and inflammation.

Pollutants, microbiota and immune system: frenemies within the gut.

Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote several pathologies through different molecular mechanisms. Pollutants can affect the immune system and related pathways, perturbing its regulation and triggering pro-inflammatory responses. The exposure to several pollutants also leads to alterations in gut microbiota with a decreasing abundance of beneficial microbes, such as short-chain fatty acid-producing bacteria, and an overgrowth of pro-inflammatory species. The subsequent intestinal barrier dysfunction, together with oxidative stress and increased inflammatory responses, plays a role in the pathogenesis of gastrointestinal inflammatory diseases. Moreover, pollutants encourage the inflammation-dysplasia-carcinoma sequence through various mechanisms, such as oxidative stress, dysregulation of cellular signalling pathways, cell cycle impairment and genomic instability. In this narrative review, we will describe the interplay between pollutants, gut microbiota, and the immune system, focusing on their relationship with inflammatory bowel diseases and colorectal cancer. Understanding the biological mechanisms underlying the health-to-disease transition may allow the design of public health policies aimed at reducing the burden of disease related to pollutants.

Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer—A Narrative Review

Non-coding RNAs (ncRNAs) represent a broad family of molecules that regulate gene expression, including microRNAs, long non-coding RNAs and circular RNAs, amongst others. Dysregulated expression of ncRNAs alters gene expression, which is implicated in the pathogenesis of several malignancies and inflammatory diseases. Gastric cancer is the fifth most frequently diagnosed cancer and the fourth most common cause of cancer-related death. Studies have found that altered expression of ncRNAs may contribute to tumourigenesis through regulating proliferation, apoptosis, drug resistance and metastasis. This review describes the potential use of ncRNAs as diagnostic and prognostic biomarkers. Moreover, we discuss the involvement of ncRNAs in the pathogenesis of gastric cancer, including their interactions with the members of major signalling pathways.

Construction of a screening system for lipid-derived radical inhibitors and validation of hit compounds to target retinal and cerebrovascular diseases

Recent studies have highlighted the indispensable role of oxidized lipids in inflammatory responses, cell death, and disease pathogenesis. Consequently, inhibitors targeting oxidized lipids, particularly lipid-derived radicals critical in lipid peroxidation, which are known as radical-trapping antioxidants (RTAs), have been actively pursued. We focused our investigation on nitroxide compounds that have rapid second-order reaction rate constants for reaction with lipid-derived radicals. A novel screening system was developed by employing competitive reactions between library compounds and a newly developed profluorescence nitroxide probe with lipid-derived radicals to identify RTA compounds. A PubMed search of the top hit compounds revealed their wide application as repositioned drugs. Notably, the inhibitory efficacy of methyldopa, selected from these compounds, against retinal damage and bilateral common carotid artery stenosis was confirmed in animal models. These findings underscore the efficacy of our screening system and suggest that it is an effective approach for the discovery of RTA compounds.

Keratin 17- and PKCα-dependent amplification of neutrophil influx after repeated stress to skin

Abstract Neutrophils contribute to the pathogenesis of chronic inflammatory skin diseases. Little is known about the source and identity of the signals mediating their recruitment in inflamed skin. We used the phorbol ester TPA and UVB, alone or in combination, to induce sterile inflammation in mouse skin and assess whether keratinocyte-derived signals impact neutrophil recruitment. A single TPA treatment results in a neutrophil influx in the dermis that peaks at 12h and resolves within 24h. A second TPA treatment or a UVB challenge, when applied at 24h but not 48h later, accelerates, amplifies, and prolongs neutrophil infiltration. This transient amplification response (TAR) is mediated by local signals in inflamed skin, can be recapitulated in ex vivo culture, and involves the K17-dependent sustainment of Protein Kinase C α (PKCα) activity and release of neutrophil chemoattractants by stressed keratinocytes. We show that K17 binds RACK1, an essential scaffolding protein for PKCα activity. Analyses of RNAseq data reveal the presence of a transcriptomic signature consistent with TAR and PKCα activation in chronic inflammatory skin diseases including psoriasis, hidradenitis suppurativa, and atopic dermatitis. These findings uncover a novel, transient, and keratin-dependent mechanism that amplifies neutrophil recruitment to the skin under stress, with direct implications for inflammatory skin disorders.

Gout, hyperuricemia and NLRP3 inflammasome: a literature review

Gout is a form of self-limiting inflammatory arthritis caused by hyperuricemia and the deposition of monosodium urate (MSU) crystals in joint tissues. This deposition causes the activation of the NLRP3 inflammasome, thus triggering an inflammatory cascade. Intense activation of the NLRP3 inflammasome is associated with the pathogenesis of several inflammatory diseases, including gout. For this reason, this inflammasome has become a potential target for controlling this type of inflammation. In this review, 33 publications were selected from the Google Scholar, Scielo and PubMed platforms, thus providing a comprehensive perspective on the condition of gout and its relationship with the NLRP3 inflammasome. This review provides a broad view of the inflammatory process associated with gout, focusing on the NLRP3 inflammasome. In this context, interventions targeting these inflammasome and IL-1 pathways appear promising for the treatment of this disease.

Important Roles of Interleukin-36, Interleukin-37, and Interleukin-38 Cytokines in the Pathogenesis of Rosacea.

Rosacea is a chronic inflammatory skin disease. Previous studies have determined that IL-36, IL-37, and IL-38 may play a role in the pathogenesis of various inflammatory diseases. The present study aims to evaluate the relationship of these cytokines with rosacea. A total of 100 individuals, including 50 patients with rosacea and 50 healthy controls, were included in the study. IL-36, IL-37, and IL-38 levels were measured using the ELISA method by taking serum samples from all participants. The mean serum levels of IL-36, IL-37, and IL-38 in the patient group were 52.17 ± 24.07 pg/ml, 18.46 ± 8.18 pg/ml, and 25.74 ± 8.36 ng/l, respectively. The mean serum levels of IL-36, IL-37, and IL-38 in the control group were 32.99 ± 19.90 pg/ml, 44.61 ± 22.27 pg/ml, and 45.61 ± 17.32 ng/l, respectively. The difference between the serum levels of IL-36, IL-37, and IL-38 in the patient and control groups was statistically significant (P < 0.001). Based on these findings, an increase in IL-36 and a decrease in IL-37 and IL-38 may contribute to the pathogenesis of rosacea. Future rosacea treatments could target and/or interact with these possible steps in the pathogenesis of rosacea.

Serum Levels of IL-35, One of the Newest Members of Interleukin-12 Family of Cytokines, in Patients With Vitiligo.

Vitiligo is a chronic skin disorder in which immune dysregulation has been reported as one of the major etiopathological factors. Interleukin-12 (IL-12), IL-23 and IL-27 of IL-12 cytokine family were identified as critical cytokines in the pathogenesis of many autoimmune and inflammatory skin diseases including vitiligo. IL-35 is one of the newest member of IL-12 cytokine family. The purpose of our study was to examine serum IL-35 levels in addition to serum IL-12, IL-23, IL-27 levels in the vitiligo patients and control group, and to investigate the relationship of these cytokines with the characteristics of vitiligo. Serum IL-12, IL-23, IL-27 and IL-35 levels of 87 vitiligo patients and 70 healthy volunteers were analyzed using the enzyme-linked immunosorbent assay (ELISA). We compared the IL-12 cytokine family levels in the patient and control groups, and investigated the relationship of these levels with the characteristics of vitiligo. Patients had higher levels of IL-12 (31.2 versus 20.1, P < 0.001) and IL-35 (9.6 versus 8.1, P = 0.031). Patient and control groups had similar levels of IL-23 (P = 0.78) but were correlated with the Vitiligo Area Scoring Index (VASI) (P = 0.022, r = 0.35). Patients had lower levels of IL-27 (207.6 versus 258.7, P < 0.001). In addition, the levels of serum IL-27 were correlated negatively with the Vitiligo Disease Activity (VIDA), and positively with disease duration (P = 0.007, r = 0.30). Differences of serum levels between Vitiligo patients and healthy controls, significant relationships with the characteristics of vitiligo suggest that the IL-12 cytokine family may play a role in the pathogenesis of vitiligo.

Fibroblast expression of neurotransmitter receptor HTR2A associates with inflammation in rheumatoid arthritis joint

The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related conditions. One important mode of cell-to-cell communication in the synovial fluid (SF) is through extracellular vesicles (EVs) carrying microRNAs (miRNAs). The role of neurotransmitter receptors in the pathogenesis of inflammatory joint diseases, and whether there are specific miRNAs regulating differentially expressed HTR2A, contributing to the inflammatory processes and bone metabolism is unclear. Expression of neurotransmitter receptors and their correlated inflammatory molecules were identified in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium from a scRNA-seq dataset. Immunohistochemistry staining of synovial tissue (ST) from RA and OA patients was performed for validation. Expression of miRNAs targeting HTR2A carried by SF EVs was screened in low- and high-grade inflammation RA from a public dataset and validated by qPCR. HTR2A reduction by target miRNAs was verified by miRNAs mimics transfection into RA fibroblasts. HTR2A was found to be highly expressed in fibroblasts derived from RA synovial tissue. Its expression showed a positive correlation with the degree of inflammation observed. 5 miRNAs targeting HTR2A were decreased in RA SF EVs compared to OA, three of which, miR-214-3p, miR-3120-5p and miR-615-3p, mainly derived from monocytes in the SF, were validated as regulators of HTR2A expression. The findings suggest that fibroblast HTR2A may play a contributory role in inflammation and the pathogenesis of RA. Additionally, targeting miRNAs that act upon HTR2A could present novel therapeutic strategies for alleviating inflammation in RA.

Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties.

Several studies in animal models and human cohorts have recently suggested that HDLs (high-density lipoproteins) not only modulate innate immune responses but also adaptative immune responses, particularly CD4+ T cells. CD4+ T cells are central effectors and regulators of the adaptive immune system, and any alterations in their homeostasis contribute to the pathogenesis of cardiovascular diseases, autoimmunity, and inflammatory diseases. In this review, we focus on how HDLs and their components affect CD4+ T-cell homeostasis by modulating cholesterol efflux, immune synapsis, proliferation, differentiation, oxidative stress, and apoptosis. While the effects of apoB-containing lipoproteins on T cells have been relatively well established, this review focuses specifically on new connections between HDL and CD4+ T cells. We present a model where HDL may modulate T cells through both direct and indirect mechanisms.

Acetyl-CoA-dependent ac4C acetylation promotes the osteogenic differentiation of LPS-stimulated BMSCs

The impaired osteogenic capability of bone marrow mesenchymal stem cells (BMSCs) caused by persistent inflammation is the main pathogenesis of inflammatory bone diseases. Recent studies show that metabolism is disturbed in osteogenically differentiated BMSCs in response to Lipopolysaccharide (LPS) treatment, while the mechanism involved remains incompletely revealed. Herein, we demonstrated that BMSCs adapted their metabolism to regulate acetyl-coenzyme A (acetyl-CoA) availability and RNA acetylation level, ultimately affecting osteogenic differentiation. The mitochondrial dysfunction and impaired osteogenic potential upon inflammatory conditions accompanied by the reduced acetyl-CoA content, which in turn suppressed N4-acetylation (ac4C) level. Supplying acetyl-CoA by sodium citrate (SC) addition rescued ac4C level and promoted the osteogenic capacity of LPS-treated cells through the ATP citrate lyase (ACLY) pathway. N-acetyltransferase 10 (NAT10) inhibitor remodelin reduced ac4C level and consequently impeded osteogenic capacity. Meanwhile, the osteo-promotive effect of acetyl-CoA-dependent ac4C might be attributed to fatty acid oxidation (FAO), as evidenced by activating FAO by L-carnitine supplementation counteracted remodelin-induced inhibition of osteogenesis. Further in vivo experiments confirmed the promotive role of acetyl-CoA in the endogenous bone regeneration in rat inflammatory mandibular defects. Our study uncovered a metabolic-epigenetic axis comprising acetyl-CoA and ac4C modification in the process of inflammatory osteogenesis of BMSCs and suggested a new target for bone tissue repair in the context of inflammatory bone diseases.

Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD.

Chronic inflammatory and immune responses play key roles in the development and progression of chronic obstructive pulmonary disease (COPD). PANoptosis, as a unique inflammatory cell death modality, is involved in the pathogenesis of many inflammatory diseases. We aim to identify critical PANoptosis-related biomarkers and explore their potential effects on respiratory tract diseases and immune infiltration landscapes in COPD. Total microarray data consisting of peripheral blood and lung tissue datasets associated with COPD were obtained from the GEO database. PANoptosis-associated genes in COPD were identified by intersecting differentially expressed genes (DEGs) with genes involved in pyroptosis, apoptosis, and necroptosis after normalizing and removing the batch effect. Furthermore, GO, KEGG, PPI network, WGCNA, LASSO-COX, and ROC curves analysis were conducted to screen and verify hub genes, and the correlation between PYCARD and infiltrated immune cells was analyzed. The effect of PYCARD on respiratory tract diseases and the potential small-molecule agents for the treatment of COPD were identified. PYCARD expression was verified in the lung tissue of CS/LPS-induced COPD mice. PYCARD was a critical PANoptosis-related gene in all COPD patients. PYCARD was positively related to NOD-like receptor signaling pathway and promoted immune cell infiltration. Moreover, PYCARD was significantly activated in COPD mice mainly by targeting PANoptosis. PANoptosis-related gene PYCARD is a potential biomarker for COPD diagnosis and treatment.

Increased Serum Apelin Levels in Patients with Inflammatory Bowel Disease

Apelin has been implicated in the pathogenesis of several chronic inflammatory diseases through mechanisms related to endothelial cells dysfunction. There is evidence of increased apelin levels in mesenteric adipose tissue and colonic epithelium in patients with inflammatory bowel disease (IBD), but their significance remains unclear. We aimed to measure serum apelin (SA) levels in patients with IBD and to evaluate an association with disease characteristics. SA levels of 104 IBD patients and age and sex matched healthy controls (HCs) in a 1:1 ratio were compared. SA-13 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Mean SA levels were increased in IBD patients compared to HCs (1996.29 ± 1592.96 pg/mL vs. 1552.99 ± 809.64 pg/mL, p = 0.012). Both patients without and with cardiovascular disease (CVD) had increased SA levels (2076.44 ± 1714.74 pg/mL vs. 1525.75 ± 818.74 pg/mL, p = 0.011 and 1743.01 ± 1116.26 pg/mL vs. 1283.92 ± 726.85 pg/mL, p = 0.035, respectively). An inverse association between mean SA levels and a history of musculoskeletal extraintestinal manifestations in the subgroup of IBD patients without CVD was found (p = 0.043). The present study—the first to evaluate SA levels in patients with IBD—showed that IBD patients have higher levels of SA compared to HCs. The potential role of SA in IBD merits further investigation in larger studies.

Arginase inhibitor reduces fungal dissemination in murine pulmonary cryptococcosis by promoting anti-cryptococcal immunity

Elevation of arginase enzyme activity in the lung contributes to the pathogenesis of various chronic inflammatory diseases and infections. Inhibition of arginase expression and activity is able to alleviate those effects. Here, we investigated the immunomodulatory effect of arginase inhibitor in C. neoformans infection. In the pulmonary cryptococcosis model that was shown to recapitulate human infection, we found arginase expression was excessively induced in the lung during the late stage of infection. To inhibit the activity of arginase, we administered a specific arginase inhibitor, nor-NOHA, during C. neoformans infection. Inhibition of arginase reduced eosinophil infiltration and level of IL-13 secretion in the lungs. Whole lung transcriptome RNA-sequencing analysis revealed that treatment with nor-NOHA resulted in shifting the Th2-type gene expression patterns induced by C. neoformans infection to the Th1-type immune profile, with higher expression of cytokines Ifng, Il6, Tnfa, Csf3, chemokines Cxcl9 and Cxcl10 and transcription factor Stat1. More importantly, mice treated with arginase inhibitor had more infiltrating brain leukocytes and enhanced gene expression of Th1-associated cytokines and chemokines that are known to be essential for protection against C. neoformans infection. Inhibition of arginase dramatically attenuated spleen and brain infection, with improved survival. Taken together, these studies demonstrated that inhibiting arginase activity induced by C. neoformans infection can modulate host immune response by enhancing protective type-1 immune response during C. neoformans infection. The inhibition of arginase activity could be an immunomodulatory target to enhance protective anti-cryptococcal immune responses.

Inflammatory liver diseases and susceptibility to sepsis.

Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis.

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets.

Cutaneous T cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at the clinical and therapeutic levels regarding the most well-known inflammatory mediators. An in-depth look is given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression. From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major interleukins known in inflammatory environments. Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL. In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

The contribution of the WNT pathway to the therapeutic effects of montelukast in experimental murine airway inflammation induced by ovalbumin and lipopolysaccharide.

The wingless/integrase-1 (WNT) pathway involved in the pathogenesis of inflammatory airway diseases has recently generated considerable research interest. Montelukast, a leukotriene receptor antagonist, provides therapeutic benefits in allergic asthma involving eosinophils. We aimed to investigate the role of the WNT pathway in the therapeutic actions of montelukast (MT) in a mixed type of allergic-acute airway inflammation model induced by ovalbumin (OVA) and lipopolysaccharide (LPS) in mice. Female mice were sensitized with intraperitoneal OVA-Al(OH)3 administration in the initiation phase and intranasal OVA followed by LPS administration in the challenge phase. The mice were divided into eight groups: control, asthmatic, and control/asthmatic treated with XAV939 (inhibitor of the canonical WNT pathway), LGK-974 (inhibitor of the secretion of WNT ligands), or MT at different doses. The inhibition of the WNT pathway prevented tracheal 5-HT and bradykinin hyperreactivity, while only the inhibition of the canonical WNT pathway partially reduced 5-HT and bradykinin contractions compared to the inflammation group. Therefore, MT treatment hindered 5-HT and bradykinin hyperreactivity associated with airway inflammation. Furthermore, MT prevented the increases in the phosphorylated GSK-3β and WNT5A levels, which had been induced by airway inflammation, in a dose-dependent manner. Conversely, the MT application caused a further increase in the fibronectin levels, while there was no significant alteration in the phosphorylation of the Smad-2 levels in the isolated lungs of the mice. The MT treatment reversed the increase in the mRNA expression levels of interleukin-17A. An increase in eosinophil and neutrophil counts was observed in bronchoalveolar lavage fluid samples obtained from the mice in the inflammation group, which was hampered by the MT treatment. The inhibition of the WNT pathway did not alter inflammatory cytokine expression or cell infiltration. The WNT pathway mediated the therapeutic effects of MT due to the inhibition of GSK-3β phosphorylation as well as the reduction of WNT5A levels in a murine airway inflammation model.

Identification and validation of immune-related genes in osteoarthritic synovial fibroblasts

ObjectiveOA was generally considered as a non-inflammatory disease dominated by articular cartilage degeneration. However, the role of synovitis in OA pathogenesis has received increasing attention. Recent studies support that OA patients have a pro-inflammatory/catabolic synovial environment similar to RA patients, promoting the occurrence and development of OA. Therefore, we investigated the co-immune-related genes and pathways of OA and RA to explore whether part of the pathogenesis of RA synovitis can be used to explain OA synovitis. MethodsData of GSE29746 and GSE12021 were downloaded from the Gene Expression Omnibus (GEO) database. Compared with control group, differentially expressed genes (DEGs) of OA and RA groups were screened separately by R software, Venny website was used to screen co-DEGs. Metascape was used to screen the common enriched terms and pathways between OA and RA. STRING website and Cytoscape software were used to map protein–protein interaction (PPI) networks and screen co-hub genes. GSE29746 was selected as the test dataset, and GSE12021 as the validation dataset for validate the co-hub genes. The results were validated by western blotting (WB) and real-time quantitative polymerase chain reaction (qPCR) of clinical synovial samples. ResultsWe identified 573 OA-related DEGs, 148 RA-related DEGs, and 52 co-DEGs, revealing 14 common enriched terms, most of which were related to immune inflammation. IL7R was the only upregulated co-hub gene between OA and RA in the PPI network, consistent with the validation dataset. IL7R was highly expressed in clinical osteoarthritic synovial samples (P < 0.001). ConclusionOur findings suggested that IL7R is a critical co-DEG in OA and RA and confirmed the involvement of immune inflammation in disease pathogenesis. Furthermore, it confirms the role of IL7R in synovial inflammation in RA and OA synovitis and provides evidence for further investigation of OA immune inflammation.