白细胞介素-6信号诱导滑膜成纤维细胞和巨噬细胞中因子XIII的表达。

IF 5 3区 医学 Q2 IMMUNOLOGY Inflammation and Regeneration Pub Date : 2023-01-06 DOI:10.1186/s41232-022-00252-4
Hirofumi Watanabe, Sho Mokuda, Tadahiro Tokunaga, Hiroki Kohno, Michinori Ishitoku, Kei Araki, Tomohiro Sugimoto, Yusuke Yoshida, Toshihiro Yamamoto, Mayuko Matsumoto, Junya Masumoto, Shintaro Hirata, Eiji Sugiyama
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引用次数: 3

摘要

背景:凝血因子XIII (FXIII)在凝血级联的最后阶段促进纤维蛋白分子之间的交联。然而,其在细胞或组织中的表达和功能,特别是因子XIII亚基B (FXIII-B)仍然存在争议。类风湿性关节炎(RA)患者在抗白细胞介素-6 (IL-6)受体抗体治疗后出现出血性FXIII缺乏症。与接受其他生物制剂治疗的患者相比,接受这种生物制剂的患者FXIII活性降低。促炎细胞因子与FXIII表达之间的关系尚不清楚。方法:采用免疫组化、RT-qPCR、western blotting等方法研究FXIII在滑膜组织中的表达规律。用重组IL-6和抗IL-6受体抗体处理表达FXIII-A的单核细胞源性巨噬细胞。对过表达FXIII-B的细胞进行RNA测序以阐明FXIII-B的功能。结果:滑膜组织免疫组化分析显示,因子XIII亚单位A (FXIII-A)在M2巨噬细胞中表达,FXIII-B在成纤维细胞样滑膜细胞中表达。IL-6刺激上调il -4诱导的单核细胞源性巨噬细胞中FXIII-A的表达,抗IL-6受体抗体抑制FXIII-A的表达。FXIII-B在成纤维细胞样滑膜细胞上清液中的分泌量高于其他细胞。RNA测序结果显示,FXIII-B上调了抗凋亡分子和趋化因子相关基因的表达。结论:我们的研究结果强调滑膜组织是FXIII产生的来源之一。我们还证明了il -6依赖性FXIII-A表达和FXIII-B的新潜在功能。
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Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling.

Background: Blood 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.

Methods: To 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.

Results: The 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.

Conclusions: Our 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.

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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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