The emerging role of irisin in experimentally induced arthritis: a recent update involving HMGB1/MCP1/Chitotriosidase I–mediated necroptosis

Ibrahim, Rowida Raafat; Shafik, Noha M.; El‐Esawy, Rasha Osama; El‐Sakaa, Mervat H.; Arakeeb, Heba M; Elsharaby, Radwa Mahmoud; Ali, Dina; El-Deeb, Omnia Safwat; El-Khalik, Sara Ragab Abd

doi:10.1080/13510002.2022.2031516

Cited by 11 publications

(9 citation statements)

References 51 publications

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“…The level of S100A8/A9 was signi cantly higher than that in the non-RA group and the healthy control group, indicating that in the in ammatory joint disease, HMGB1, SII, S100A8/A9 and MCP-1 indeed increased signi cantly, not only in the RA patients. Among them, S100A8 / A9 increased signi cantly in the RA patients (P 0.01), which was similar to the results of Ibrahim-R Raafat et al [23] .…”

Section: Discussionsupporting

confidence: 89%

To explore the application of HMGB1, SII, S100A8 / A9 and MCP-1 in the diagnosis, condition monitoring and prognosis of rheumatoid arthritis

Xiang

Zhang²,

Lai³

et al. 2022

Preprint

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Objective: To explore the diagnosis and prognosisvalue of high mobility group box1 protein B1(HMGB1), systemic immune inflammatory index (SII), calcium binding proteinA8/A9 complex (S100A8/ A9) and monocyte chemoattractant protein-1 (MCP-1) in rheumatoid arthritis (RA). Methods: From January 2020 to December 2021, 154 patients diagnosed with RA in the outpatient and inpatient clinics of the Second Affiliated Hospital of Nanchang University and Yingtan People's Hospital were selected as the RA group, A total of 303 cases including 78 cases of Sjogren's syndrome (SS), 62 cases of systemic lupus erythematosus (SLE), 79 cases of ankylosing spondylitis (AS) and 84 cases of osteoarthritis (OA) were selected as as a non-RA group, and 43 healthy people who underwent physical examination at the same time in the hospital were selected as the healthy control group.The levels of HMGB1, S100A8/A9 and MCP-1 were detected by enzyme-linked immunosorbent assay (ELISA), platelets (PLT) and lymphocytes (L) were detected by sheath flow electrical impedance method, neutrophils (N) were detected by flow cytometry combined with fluorescence staining,(N), calculate SII and detect other laboratory indicators.The disease activity index 28 (DAS28) score was used to evaluate the disease activity of RA and the efficacy after treatment,the patients with RA were followed up at 1 month, 2 months and 3 months after treatment, and the correlation between the detection indicators in each period was analyzed. Results: ① the levels of HMGB1, SII, S100A8/A9 and MCP-1 in RA group were significantly higher than those in healthy control group (P < 0.01),and the AUC area of RA diagnosis was 0.86, 0.79, 0.84 and 0.80, respectively, the AUC area of HMGB1 was the largest. ② The positive rates of HMGB1, SII, S100A8 / A9 and MCP-1 in RF (-) and Anti-CCP (-) groups were 37.50%, 37.50%, 50.00% and 62.5%, respectively. The positive rate of MCP-1 was the highest. ③ The levels of HMGB1, S100A8 / A9 and MCP-1 in high disease activity group and middle disease activity group were higher than those in low disease activity group, remission group and healthy control group (P < 0.05).④ HMGB1, SII, S100A8 / A9 and MCP-1 were positively correlated with DSA28 score (r= 0.476, 0.286, 0.522 and 0.441, respectively, P < 0.01); Δ HMGB1, Δ SII, Δ S100A8 / A9 and Δ MCP-1 and Δ DAS28 before and after treatment in RA patients was positively correlated (r = 0.628, 0.524, 0.603 and 0.579, P < 0.01). Conclusion: HMGB1, SII, S100A8/A9 and MCP-1 show better diagnostic performance in RA, especially improving the detected rate of RF (-) and Anti-CCP (-) RA patients;Besides,HMGB1, SII, S100A8/A9 and MCP-1 can be used for disease activity monitoring and disease evaluation of RA patients.

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Section: Discussionsupporting

confidence: 89%

To explore the application of HMGB1, SII, S100A8 / A9 and MCP-1 in the diagnosis, condition monitoring and prognosis of rheumatoid arthritis

Xiang

Zhang²,

Lai³

et al. 2022

Preprint

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“…Accumulating documents have recognized necroptosis as a crucial downstream target of the inflammatory process during RA progression, suggesting that necroptosis acts as an important regulator for RA 34,36 . Meanwhile, RIPK3 and MLKL were discovered to be highly expressed in RA patients and have been suggested to be promising therapeutic targets for the treatment of RA 37,38 . As expected, a triggered necroptosis and high levels of RIPK3 and MLKL proteins were discovered in LPS‐mediated C28/I2 cells in this study, while these elevations were greatly inhibited by BIRC2 knockdown, suggesting that BIRC2 knockdown could repress LPS‐caused necroptosis in C28/I2 cells.…”

Section: Discussionsupporting

confidence: 79%

“…34,36 Meanwhile, RIPK3 and MLKL were discovered to be highly expressed in RA patients and have been suggested to be promising therapeutic targets for the treatment of RA. 37,38 As expected, a triggered necroptosis and high levels of RIPK3 and MLKL proteins were discovered in LPS-mediated C28/I2 cells in this study, while these elevations were greatly inhibited by BIRC2 knockdown, suggesting that BIRC2 knockdown could repress LPS-caused necroptosis in C28/I2 cells. In addition, TRADD has been demonstrated to mediate RIPK1-dependent necroptosis by regulating the RIPK3-MLKL pathway, highlighting the critical role of TRADD in regulating necroptosis, 39 which was also reflected in the present study that TRADD overexpression greatly weakened the inhibitory effect of BIRC2 knockdown on necroptosis in LPSmediated C28/I2 cells.…”

Section: Discussionsupporting

confidence: 75%

Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD

Rao,

Xu,

et al. 2023

Immunity Inflam & Disease

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AimRheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat‐containing 2 (BIRC2) and tumor necrosis factor receptor 1‐associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA.MethodsC28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real‐time polymerase chain reaction and western blot. Cell Counting Kit‐8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro‐inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co‐immunoprecipitation assay.ResultsBIRC2 and TRADD were discovered to be highly expressed in LPS‐mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS‐induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS‐mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression.ConclusionIn summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS‐mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA.

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“…Recent research utilising rats with experimental arthritis showed that irisin has therapeutic potential due to its anti-inflammatory and antioxidant actions [423]. Furthermore, RA patients had substantially reduced irisin levels in their serum when compared to healthy controls [342,349,350], and irisin levels were significantly inversely correlated with disease activity and disability in RA patients [342,349] (Table 5).…”

Section: Irisinmentioning

confidence: 99%

Adipokines in Rheumatoid Arthritis: Emerging Biomarkers and Therapeutic Targets

Bilski,

Schramm-Luc,

Szczepanik

et al. 2023

Biomedicines

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Rheumatoid arthritis (RA) is a chronic inflammatory disease manifested by joint involvement, extra-articular manifestations, and general symptoms. Adipose tissue, previously perceived as an inert energy storage organ, has been recognised as a significant contributor to RA pathophysiology. Adipokines modulate immune responses, inflammation, and metabolic pathways in RA. Although most adipokines have a pro-inflammatory and aggravating effect on RA, some could counteract this pathological process. The coexistence of RA and sarcopenic obesity (SO) has gained attention due to its impact on disease severity and outcomes. Sarcopenic obesity further contributes to the inflammatory milieu and metabolic disturbances. Recent research has highlighted the intricate crosstalk between adipose tissue and skeletal muscle, suggesting potential interactions between these tissues in RA. This review summarizes the roles of adipokines in RA, particularly in inflammation, immune modulation, and joint destruction. In addition, it explores the emerging role of adipomyokines, specifically irisin and myostatin, in the pathogenesis of RA and their potential as therapeutic targets. We discuss the therapeutic implications of targeting adipokines and adipomyokines in RA management and highlight the challenges and future directions for research in this field.

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The emerging role of irisin in experimentally induced arthritis: a recent update involving HMGB1/MCP1/Chitotriosidase I–mediated necroptosis

Cited by 11 publications

References 51 publications

To explore the application of HMGB1, SII, S100A8 / A9 and MCP-1 in the diagnosis, condition monitoring and prognosis of rheumatoid arthritis

To explore the application of HMGB1, SII, S100A8 / A9 and MCP-1 in the diagnosis, condition monitoring and prognosis of rheumatoid arthritis

Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD

Adipokines in Rheumatoid Arthritis: Emerging Biomarkers and Therapeutic Targets

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