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

ABSTRACT

Objectives

Necroptosis is a tightly adjusted inflammatory necrotizing cell death signaling pathway that participates in pathogenesis of discrete diseases as rheumatoid arthritis (RA). Irisin is a myokine with immuno-modulatory effect. Evaluation of irisin efficiency as a novel therapeutic agent in experimentally induced RA via modulating immuno-inflammatory, necroptotic molecular and biochemical signaling pathways.

Methods

RA was induced in 30 female Wister albino rats by a single subcutaneous injection of collagen-II with incomplete Freund’s adjuvant (CII-IFA) followed by booster immunization dose 10 days later. After 14 days of the injection, arthritis chronic phase was precipitated. 15 rats were treated by S.C irisin injection daily for 4 weeks. Joint tissue homogenate RIPK-3, MLKL, HMGB1, MCP1, IL-6, CHIT1, MDA, and PN levels were assessed calorimetrically. However, TNF-α mRNA expression level was evaluated by the qrt-PCR technique.

Results

The results showed that irisin significantly decreases the level of all assessed biochemical parameters, except MDA, which was significantly increased in comparison with the correspondent values in the arthritic group with no treatment (ttt).

Conclusions

Irisin exhibits therapeutic anti-inflammatory and antioxidant effects via modulating immuno-inflammatory, necroptotic molecular, and biochemical signaling pathways in experimentally induced RA in rats.

Abbreviations

RA: rheumatoid arthritis; RIPK3: receptor-interacting protein kinase 1; MLKL: mixed lineage kinase domain-like protein; HMGB1: High-mobility group protein box 1; MCP1: Monocyte chemoattractant protein 1; IL-6: Interleukin 6; CHIT1: Chitotriosidase; MDA: Malondialdehyde; PN: Peroxynitrite; TNF-α: Tumor Necrosis Factor; qrt-PCR: quantitative real-time reverse transcription PCR; CII-IFA: collagen-II with incomplete Freund’s adjuvant; ttt: treatment

Note: TNF-α gene (NCBI GenBank Nucleotide accession # NM_012675.3); The housekeeping gene GAPDH (NCBI GenBank Nucleotide accession # NM_017008.4)

KEYWORDS:

• Arthritis
• Irisin
• high-mobility group box 1
• necroptosis
• Monocyte chemoattractant protein 1
• RIPK1/3
• ‌Chitotriosidase-1

Acknowledgements

We would like to acknowledge Prof. Dr. Dareen Abd Elaziz Mohamed, Pathology Department, Faculty of Medicine, Tanta University, for her valuable help with regard to the light microscopic histopathological examination and immunohistochemical evaluation in the present work.

Authors contribution

Rowida Raafat carried out the formal analysis; Rowida Raafat, Rasha el esawy, Mervat el sakaa, Radwa sharaby, Noha Shafek, Omnia Safwat, and Sara Ragab devised the methodology; Sara Ragab, Rasha el esawy, Omnia Safwat, and Mervat el sakaa wrote the original draft; Rowida Raafat did the review and editing; Rowida Raafat, Mervat el sakaa, and Dina Adam Ali conducted the statistical analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Research involving animals

All procedures performed in studies involving animals were in accordance with the ethical standards of the Animal Care Ethical Committee guidelines of the Faculty of Medicine, Tanta University.

Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).