Interleukin-6 plays a critical role in aldosterone-induced macrophage recruitment and infiltration in the myocardium.

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.

• 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
• Journal: Biochimica et biophysica acta. Molecular basis of disease (Biochim Biophys Acta Mol Basis Dis) Vol. 1866 Issue 3 Pg. 165627 (03 01 2020) ISSN: 1879-260X [Electronic] Netherlands
• PMID: 31785407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• IL6 protein, human
• Interleukin-6
• interleukin-6, mouse
• Aldosterone

Topics

• Aldosterone (pharmacology)
• Animals
• Cell Line, Tumor
• Fibrosis (metabolism)
• Humans
• Interleukin-6 (metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardium (metabolism)
• Signal Transduction (drug effects, physiology)
• THP-1 Cells