Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling
Abstract 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 FX...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Inflammation and Regeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41232-022-00252-4 |
| _version_ | 1797958805613445120 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hirofumi Watanabe |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T00:23:58Z |
| format | Article |
| id | doaj.art-66ed8a674d6348bbaa2507035089de7a |
| institution | Directory Open Access Journal |
| issn | 1880-8190 |
| language | English |
| last_indexed | 2024-04-11T00:23:58Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Inflammation and Regeneration |
| spelling | doaj.art-66ed8a674d6348bbaa2507035089de7a2023-01-08T12:07:05ZengBMCInflammation and Regeneration1880-81902023-01-0143111510.1186/s41232-022-00252-4Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signalingHirofumi Watanabe0Sho Mokuda1Tadahiro Tokunaga2Hiroki Kohno3Michinori Ishitoku4Kei Araki5Tomohiro Sugimoto6Yusuke Yoshida7Toshihiro Yamamoto8Mayuko Matsumoto9Junya Masumoto10Shintaro Hirata11Eiji Sugiyama12Department of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Pathology, Ehime University Proteo-Science Center and Graduate School of MedicineDepartment of Pathology, Ehime University Proteo-Science Center and Graduate School of MedicineDepartment of Pathology, Ehime University Proteo-Science Center and Graduate School of MedicineDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalDepartment of Clinical Immunology and Rheumatology, Hiroshima University HospitalAbstract 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.https://doi.org/10.1186/s41232-022-00252-4Rheumatoid arthritisBlood coagulation factor XIIIMonocyte-derived macrophagesFibroblast-like synoviocytes (FLS)Interleukin-6 |
| spellingShingle | 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 Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling Inflammation and Regeneration Rheumatoid arthritis Blood coagulation factor XIII Monocyte-derived macrophages Fibroblast-like synoviocytes (FLS) Interleukin-6 |
| title | Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling |
| title_full | Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling |
| title_fullStr | Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling |
| title_full_unstemmed | Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling |
| title_short | Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling |
| title_sort | expression of factor xiii originating from synovial fibroblasts and macrophages induced by interleukin 6 signaling |
| topic | Rheumatoid arthritis Blood coagulation factor XIII Monocyte-derived macrophages Fibroblast-like synoviocytes (FLS) Interleukin-6 |
| url | https://doi.org/10.1186/s41232-022-00252-4 |
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