https://scholars.lib.ntu.edu.tw/handle/123456789/514974
Title: | Interleukin-6 plays a critical role in aldosterone-induced macrophage recruitment and infiltration in the myocardium | Authors: | CHE-WEI LIAO Chia-Hung Chou Xue-Ming Wu ZHENG-WEI CHEN YING-HSIEN CHEN Yi-Yao Chang VIN-CENT WU Stefan Rose-John CHI-SHENG HUNG YEN-HUNG LIN TAIPAI Study Group |
Keywords: | aldosterone;interleukin 6;macrophage;matrix metalloproteinase | Issue Date: | 2020 | Publisher: | Elsevier B.V. | Journal Volume: | 1866 | Journal Issue: | 3 | Start page/Pages: | 165627 | Source: | Biochimica et Biophysica Acta - Molecular Basis of Disease | Abstract: | Macrophages play an important role in aldosterone-induced myocardial fibrosis, in which the first key steps are macrophage recruitment and infiltration. We hypothesized that IL-6 may be a key mediator of aldosterone-induced macrophage recruitment and infiltration. To test this hypothesis, we designed cell studies with a human monocytic cell line THP-1 that with monocyte/macrophage functions to explore the signaling pathway of aldosterone-induced macrophage infiltration, and further investigated the phenomenon and consequent pathway in aldosterone-infused mice studies. The results showed that aldosterone induced the expression of IL-6 via mineralocorticoid receptors, and enhanced THP-1 cell migration and infiltration. Further experiments using a protease array and siRNA revealed that expressions of MMP-1 and MMP-9 were associated with aldosterone-induced macrophage infiltration. In addition, aldosterone-induced MMP-1 and MMP-9 expressions were mediated via cyclooxygenase-II and prostaglandin E2/EP-2 and EP-4 receptors. In aldosterone-infused mice, mRNA expressions of MMP-1, MMP-9 and COX-2 in peripheral blood monocytic cells were significantly increased. Moreover, the number of mouse macrophage-restricted F4/80 protein-positive cells in the myocardium was significantly higher in the aldosterone-infused mice compared with control mice. The increase in F4/80-positive cells in the myocardium was suppressed in the aldosterone-infused mice with the aldosterone antagonist eplerenone or anti-IL-6 antibody treatment. In conclusion, interleukin-6 played an important role in aldosterone-induced macrophage recruitment and infiltration in the myocardium. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076533188&doi=10.1016%2fj.bbadis.2019.165627&partnerID=40&md5=fc37675a56525432a4f591d792979650 https://scholars.lib.ntu.edu.tw/handle/123456789/514974 |
ISSN: | 0925-4439 | DOI: | 10.1016/j.bbadis.2019.165627 |
Appears in Collections: | 醫學系 |
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