Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner
Abstract Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin‐38 (IL‐38) is a member of the IL‐1 family, which binds to IL‐36 recep...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15581 |
| _version_ | 1797397418212327424 |
|---|---|
| author | Shun Kurose Yutaka Matsubara Shinichiro Yoshino Keiji Yoshiya Koichi Morisaki Tadashi Furuyama Tomoaki Hoshino Tomoharu Yoshizumi |
| author_facet | Shun Kurose Yutaka Matsubara Shinichiro Yoshino Keiji Yoshiya Koichi Morisaki Tadashi Furuyama Tomoaki Hoshino Tomoharu Yoshizumi |
| author_sort | Shun Kurose |
| collection | DOAJ |
| description | Abstract Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin‐38 (IL‐38) is a member of the IL‐1 family, which binds to IL‐36 receptor (IL1RL2) and has an anti‐inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL‐38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II‐induced AAA model with or without IL‐38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor‐α and treated with or without IL‐38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL‐38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2+ macrophage accumulation along with matrix metalloproteinase (MMP)‐2 and ‐9 expression was observed in mouse AAA. IL‐38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP‐2 and ‐9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP‐2, and MMP‐9 production and spindle‐shaped changes were significantly suppressed by IL‐38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL‐38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL‐38 depend on the p38 pathway. IL‐38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL‐38 may be a novel therapy for AAA patients. |
| first_indexed | 2024-03-09T01:09:40Z |
| format | Article |
| id | doaj.art-7a01793d037b422486369860fa0ec2d6 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-09T01:09:40Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-7a01793d037b422486369860fa0ec2d62023-12-11T07:35:46ZengWileyPhysiological Reports2051-817X2023-01-01112n/an/a10.14814/phy2.15581Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent mannerShun Kurose0Yutaka Matsubara1Shinichiro Yoshino2Keiji Yoshiya3Koichi Morisaki4Tadashi Furuyama5Tomoaki Hoshino6Tomoharu Yoshizumi7Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Kidney Center Saiseikai Yahata General Hospital Fukuoka JapanDepartment of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDepartment of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanDivision of Respirology, Neurology and Rheumatology, Department of Medicine Kurume University School of Medicine Fukuoka JapanDepartment of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka JapanAbstract Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin‐38 (IL‐38) is a member of the IL‐1 family, which binds to IL‐36 receptor (IL1RL2) and has an anti‐inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL‐38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II‐induced AAA model with or without IL‐38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor‐α and treated with or without IL‐38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL‐38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2+ macrophage accumulation along with matrix metalloproteinase (MMP)‐2 and ‐9 expression was observed in mouse AAA. IL‐38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP‐2 and ‐9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP‐2, and MMP‐9 production and spindle‐shaped changes were significantly suppressed by IL‐38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL‐38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL‐38 depend on the p38 pathway. IL‐38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL‐38 may be a novel therapy for AAA patients.https://doi.org/10.14814/phy2.15581abdominal aortic aneurysminflammationInterleukin‐38macrophage |
| spellingShingle | Shun Kurose Yutaka Matsubara Shinichiro Yoshino Keiji Yoshiya Koichi Morisaki Tadashi Furuyama Tomoaki Hoshino Tomoharu Yoshizumi Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner Physiological Reports abdominal aortic aneurysm inflammation Interleukin‐38 macrophage |
| title | Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner |
| title_full | Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner |
| title_fullStr | Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner |
| title_full_unstemmed | Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner |
| title_short | Interleukin‐38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2‐p38 pathway‐dependent manner |
| title_sort | interleukin 38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an il1rl2 p38 pathway dependent manner |
| topic | abdominal aortic aneurysm inflammation Interleukin‐38 macrophage |
| url | https://doi.org/10.14814/phy2.15581 |
| work_keys_str_mv | AT shunkurose interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner AT yutakamatsubara interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner AT shinichiroyoshino interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner AT keijiyoshiya interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner AT koichimorisaki interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner AT tadashifuruyama interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner AT tomoakihoshino interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner AT tomoharuyoshizumi interleukin38suppressesabdominalaorticaneurysmformationinmicebyregulatingmacrophagesinanil1rl2p38pathwaydependentmanner |