Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling

Inflammation and Regeneration

Research Article

Kei Araki¹  Yusuke Yoshida¹  Hiroki Kohno¹  Michinori Ishitoku¹  Eiji Sugiyama¹  Hirofumi Watanabe¹  Tadahiro Tokunaga¹  Shintaro Hirata¹  Sho Mokuda¹  Tomohiro Sugimoto¹  Junya Masumoto²  Toshihiro Yamamoto²  Mayuko Matsumoto² 

[1] Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, 734-8551, Hiroshima, Japan;Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine, Shitsukawa, 791-0295, Toon, Ehime, Japan;

关键词: Rheumatoid arthritis;    Blood coagulation factor XIII;    Monocyte-derived macrophages;    Fibroblast-like synoviocytes (FLS);    Interleukin-6;   

DOI  :  10.1186/s41232-022-00252-4

 received in 2022-09-07, accepted in 2022-12-19,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundBlood coagulation factor XIII (FXIII) promotes cross-linking between fibrin molecules at the final stage of the blood coagulation cascade. However, its expression in cells or tissues and function, particularly factor XIII subunit B (FXIII-B), remains controversial. Hemorrhagic FXIII deficiency following anti-interleukin-6 (IL-6) receptor antibody treatment has been reported in patients with rheumatoid arthritis (RA). Patients receiving this biologics have reduced FXIII activity when compared to the activity in those treated with other biologics. The relationship between pro-inflammatory cytokines and FXIII expression remains unknown.MethodsTo investigate the expression pattern of FXIII in synovial tissues, immunohistochemistry, RT-qPCR, and western blotting were performed. FXIII-A expressed monocyte-derived macrophages were treated with recombinant IL-6 and anti-IL-6 receptor antibody. RNA sequencing of FXIII-B-overexpressing cells was performed to clarify the function of FXIII-B.ResultsThe immunohistochemical analysis of synovial tissues revealed that factor XIII subunit A (FXIII-A) was expressed in M2 macrophages, and FXIII-B was expressed in fibroblast-like synoviocytes. IL-6 stimulation upregulated FXIII-A expression in IL-4-induced monocyte-derived macrophages, and the anti-IL-6 receptor antibody suppressed FXIII-A expression. FXIII-B was more abundantly secreted in the supernatant of fibroblast-like synoviocytes compared with that of other cells. RNA sequencing showed that FXIII-B elevated the expression of genes associated with anti-apoptotic molecules and chemokines.ConclusionsOur findings highlight that synovial tissue is one of the sources of FXIII production. We also have demonstrated IL-6-dependent FXIII-A expression and the novel potential functions of FXIII-B.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2022_35_Article_IEq509.gif

41116_2022_35_Article_IEq498.gif

Fig. 25

41116_2022_35_Article_IEq485.gif

41116_2022_35_Article_IEq472.gif

41116_2022_35_Article_IEq458.gif