%0 Journal Article
%T Reciprocal Interaction between Macrophages and T cells Stimulates IFN-¦Ã and MCP-1 Production in Ang II-induced Cardiac Inflammation and Fibrosis
%A Ya-lei Han
%A Yu-lin Li
%A Li-xin Jia
%A Ji-zhong Cheng
%A Yong-fen Qi
%A Hong-jia Zhang
%A Jie Du
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0035506
%X Background The inflammatory response plays a critical role in hypertension-induced cardiac remodeling. We aimed to study how interaction among inflammatory cells causes inflammatory responses in the process of hypertensive cardiac fibrosis. Methodology/Principal Findings Infusion of angiotensin II (Ang II, 1500 ng/kg/min) in mice rapidly induced the expression of interferon ¦Ã (IFN-¦Ã) and leukocytes infiltration into the heart. To determine the role of IFN-¦Ã on cardiac inflammation and remodeling, both wild-type (WT) and IFN-¦Ã-knockout (KO) mice were infused Ang II for 7 days, and were found an equal blood pressure increase. However, knockout of IFN-¦Ã prevented Ang II-induced: 1) infiltration of macrophages and T cells into cardiac tissue; 2) expression of tumor necrosis factor ¦Á and monocyte chemoattractant protein 1 (MCP-1), and 3) cardiac fibrosis, including the expression of ¦Á-smooth muscle actin and collagen I (all p<0.05). Cultured T cells or macrophages alone expressed very low level of IFN-¦Ã, however, co-culture of T cells and macrophages increased IFN-¦Ã expression by 19.8¡À0.95 folds (vs. WT macrophage, p<0.001) and 20.9 ¡À 2.09 folds (vs. WT T cells, p<0.001). In vitro co-culture studies using T cells and macrophages from WT or IFN-¦Ã KO mice demonstrated that T cells were primary source for IFN-¦Ã production. Co-culture of WT macrophages with WT T cells, but not with IFN-¦Ã-knockout T cells, increased IFN-¦Ã production (p<0.01). Moreover, IFN-¦Ã produced by T cells amplified MCP-1 expression in macrophages and stimulated macrophage migration. Conclusions/Significance Reciprocal interaction between macrophages and T cells in heart stimulates IFN-¦Ã expression, leading to increased MCP-1 expression in macrophages, which results a forward-feed recruitment of macrophages, thus contributing to Ang II-induced cardiac inflammation and fibrosis.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035506