Role of the S100 protein family in rheumatoid arthritis

Wu, Yuanyuan; Li, Xiaofeng; Wang, Sha; Niu, Xue-Ni; Yin, Su-Qin; Huang, Cheng; Li, Jun

doi:10.1186/s13075-022-02727-8

Cited by 32 publications

(20 citation statements)

References 76 publications

(87 reference statements)

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“…NFκB is an inducible transcription factor that is expressed both in immune and non-immune cells [13]. It responds to various stimuli playing a critical role in RA, including cytokines (TNF α and IL-1β), DAMPs (HMGB1, citrullinated histones and S100 proteins) [69][70][71], molecules that bind to antigen receptors on T and B lymphocytes, and other factors such as the osteoclast differentiation factor receptor activator of NFκB ligand (RANKL) involved in osteoclast differentiation and bone destruction in RA [72].…”

Section: Redox-dependent Gene Transcription In Ramentioning

confidence: 99%

Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis

Manda

Milanesi

Genç

et al. 2022

Free Radical Biology and Medicine

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Section: Redox-dependent Gene Transcription In Ramentioning

confidence: 99%

Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis

Manda

Milanesi

Genç

et al. 2022

Free Radical Biology and Medicine

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“…Complete Freund’s adjuvant (CFA)-induced arthritis exhibits pathophysiological features similar to human RA [ 8 ], making it a useful study model [ 9 ]. The progression of RA is evidently correlated with the serum levels of various cytokines, chemokines, and growth factors [ 10 ]. Cytokines are important in RA pathogenesis because they regulate a spectrum of inflammatory processes; the imbalance between pro- and anti-inflammatory cytokines in rheumatoid joints favors the induction of autoimmunity and chronic inflammation, leading to joint destruction [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Diosmin and Trolox Have Anti-Arthritic, Anti-Inflammatory and Antioxidant Potencies in Complete Freund’s Adjuvant-Induced Arthritic Male Wistar Rats: Roles of NF-κB, iNOS, Nrf2 and MMPs

et al. 2022

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Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease caused by a malfunction of the immune system. The aim of this study was to examine the anti-arthritic effects and suggest the mechanisms of actions of diosmin and trolox in male Wistar rats. Complete Freund’s adjuvant (CFA) was used to establish RA in the animals by subcutaneous injection of 100 µL CFA/rat into plantar region of right hind leg in two consecutive days. Diosmin and/or trolox were administered orally at a dosage of 20 mg/kg/day to CFA-induced arthritic rats for 2 weeks. The normal and arthritic control groups were orally given the same equivalent volume of a vehicle (1% carboxymethyl cellulose) in which treatment agents were dissolved. At the end of the experiment, blood samples were collected from the jugular vein for the detection of the total leukocyte count (TLC) and differential leukocyte count (DLC) in blood and the detection of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), tumor necrosis factor-α (TNF-α), interleukin-13 (IL-13), and interleukin-17 (IL-17) levels by enzyme-linked immunosorbent assay (ELISA), as well as markers of oxidative stress and the antioxidant defense system in serum. The right hind ankle regions of three rats from each group were dissected out and fixed in 10% neutral-buffered formalin for histological examination and the other three were kept at −30 °C for Western blot analysis of nuclear factor-kappa B (NF-κB) protein 50 (NF-κB p50), NF-κB p65, inducible nitric oxide synthase (iNOS), nuclear factor erythroid-2-related factor 2 (Nrf2), and matrix metalloproteinase (MMP)-1 (MMP-1), MMP-3, and MMP-9. The CFA injection was deleterious to the ankle joint’s histological architecture, manifesting as infiltration of inflammatory cells into the articular cartilage, hyperplasia of the synovium, and erosion of the cartilage. All these effects were ameliorated by diosmin and/or trolox, with the combined dose being the most effective. The two compounds significantly lowered the elevated serum levels of RF, ACPA, TNF-α, and IL-17, as well as other pro-inflammatory mediators, such as NF-κB p50, NF-κB p65, iNOS, MMP-1, MMP-3 and MMP-9. They also increased the levels of the anti-inflammatory cytokine, IL-13, and the cytoprotective transcription factor Nrf2. The compounds stimulated higher activities of antioxidants, such as glutathione, glutathione-S-transferase, catalase, and superoxide dismutase, and reduced lipid peroxidation in the serum of arthritic rats. In conclusion, diosmin, trolox, and their combination, which was the most potent, exerted anti-arthritic, anti-inflammatory and antioxidant effects by suppressing NF-κB signaling, inhibiting matrix metalloproteinases, and activating Nrf2.

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“…Both S100A9 and S100A12 can regulate immune response and in ammation by inducing production of pro-in ammatory cytokines for neutrophil, monocyte and lymphocyte recruitment [30]. It was reported that S100A9 and S100A12 were signi cantly up-regulated and played an important role in pathogenesis of many in ammatory disease, such as rheumatoid, atherosclerosis and in ammatory bowel disease [31][32][33][34][35]. Although it still hasn't been widely applied in clinical diagnosis, the serum levels of S100A8/9 and S100A12 have already been proposed being potential biomarker for sJIA [7,36].…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Diagnostic Biomarkers for Systemic Juvenile Idiopathic Arthritis by Integrative Transcriptomic Analysis

Wang

et al. 2023

Preprint

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Introduction: Currently the diagnostic criteria for systemic juvenile idiopathic arthritis (sJIA) is lack of specificity. Diagnostic biomarkers are needed to be identified to help with the early diagnosis of sJIA and prevent lethal complications like MAS. The aim of this study was to identify potential diagnostic biomarkers of sJIA. Methods A JIA cohort study from Gene Expression Omnibus (GEO) database was adopted to identify hub genes of sJIA comparing to healthy or non-sJIA JIA group by using integrated bioinformatic analysis which combined differentially expressed gene (DEG) analysis, weighted co-expression network analysis (WGCNA) and protein-protein network interaction (PPI) analysis. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen out biomarker genes with most diagnostic potential for sJIA. A prediction model based on the selected genes was constructed and validated in three independent GEO cohort to testify their potency as reliable diagnostic markers to distinguish sJIA patients from healthy population as well as other different types of JIA. Also, CIBERSORT was applied to evaluate the immune cells infiltration and the correlation coefficient between three diagnostic genes and each immune cell subgroup was calculated in the correlation analysis. Results Totally 761 DEGs were acquired by comparing the gene expression profiles in peripheral blood mononuclear cell (PBMC) samples between the sJIA patients and the health controls, the up-regulated genes in sJIA group were mostly enriched in innate immunity and erythrocyte related biological process, while the down-regulated genes were mostly enriched in nature killer cells related biological process. Up to 22 hub genes were identified via combining DEGs with WGCNA and PPI network analysis. All the hub genes were processed to LASSO regression analysis and eventually three genes, 5’-Aminolevulinate Synthase 2 (ALAS2), S100 Calcium Binding Protein A9 (S100A9) and S100 Calcium Binding Protein A12 (S100A12) were screened out as the most potential diagnostic genes. The three genes-based prediction nomogram model was verified and presented good diagnostic performance in all three independent validation datasets. Erythrocyte related gene ALAS2 was with the most significance among all three genes, and specifically higher in sJIA patients comparing with the health controls and other JIA categories. Immune related genes S100A9 and S100A12 also showed significant difference in most conditions, but the difference was less dramatic when comparing with polyarthritis. ALAS2 was also highly expressed in familial hemophagocytic lymphohistiocytosis (FHLH) and systemic lupus erythematosus (SLE), which can develop to MAS and lead to hemophagocytosis. While S100A9 and S100A12 were commonly up-regulated in inflammatory disease. Conclusions ALAS2, S100A9 and S100A12 were highly relevant to sJIA and showed better performance in diagnosis of sJIA when applied comprehensively. ALAS2 may be associated with the predisposition to hemophagocytosis in sJIA, while S100A9 and S100A12 were mainly associated with the hyperinflammation.

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Role of the S100 protein family in rheumatoid arthritis

Cited by 32 publications

References 76 publications

Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis

Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis

Diosmin and Trolox Have Anti-Arthritic, Anti-Inflammatory and Antioxidant Potencies in Complete Freund’s Adjuvant-Induced Arthritic Male Wistar Rats: Roles of NF-κB, iNOS, Nrf2 and MMPs

Identification of Potential Diagnostic Biomarkers for Systemic Juvenile Idiopathic Arthritis by Integrative Transcriptomic Analysis

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