ALDOSTERONE INDUCES IL-8 PRODUCTION IN HUMAN MONONUCLEAR MACROPHAGE THROUGH MINERALOCORTICOID RECEPTOR AND TOLL-LIKE RECEPTOR-4

YAWEI CHEN¹, WEN CHEN², YUAN ZENG², XIAOHUA XIE^2*

¹PLA 254th Hospital, Tianjin 300142, China - ². First Department of Comprehensive Surgery, South building, Chinese PLA General Hospital, Beijing 100853, China

Stress and inflammation contribute to increased morbidity and mortality associated with activation of the rennin- angiotensin-aldosterone system (RAAS), learnt from our previous trauma researches. Because aldosterone has been implicated in the stimulation of cytokines production in various tissues, we investigated whether it would affect IL-8 production in cultures of human mononuclear macrophage. We first demonstrated that treatment with 10 to 104 nM aldosterone leads to a significant increase in IL-8 secretion and mRNA levels in a time-dependent manner. Pretreatment of cells with the mineralocorticoid receptor (MR) antagonist spironolactone and anti-Toll-like receptor 4 (anti-TLR4) antibody inhibited IL-8 production in aldosterone-treat- ed cultures. We also demonstrated that aldosterone increases IL-8 production by time dependent manner. We further discovered that aldosterone could regulate the protein expression of MR and TLR4. Thus, we have demonstrated for the first time that aldosterone, which stimulates IL-8 production through the MR-dependent pathway, also maybe a novel endogenous ligand to TLR4.