Reciprocal Interaction between Macrophages and T cells Stimulates IFN-γ and MCP-1 Production in Ang II-induced Cardiac Inflammation and Fibrosis
Open Access
- 2 May 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (5), e35506
- https://doi.org/10.1371/journal.pone.0035506
Abstract
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. Infusion of angiotensin II (Ang II, 1500 ng/kg/min) in mice rapidly induced the expression of interferon γ (IFN-γ) and leukocytes infiltration into the heart. To determine the role of IFN-γ on cardiac inflammation and remodeling, both wild-type (WT) and IFN-γ-knockout (KO) mice were infused Ang II for 7 days, and were found an equal blood pressure increase. However, knockout of IFN-γ prevented Ang II-induced: 1) infiltration of macrophages and T cells into cardiac tissue; 2) expression of tumor necrosis factor α and monocyte chemoattractant protein 1 (MCP-1), and 3) cardiac fibrosis, including the expression of α-smooth muscle actin and collagen I (all p<0.05). Cultured T cells or macrophages alone expressed very low level of IFN-γ, however, co-culture of T cells and macrophages increased IFN-γ expression by 19.8±0.95 folds (vs. WT macrophage, p<0.001) and 20.9 ± 2.09 folds (vs. WT T cells, p<0.001). In vitro co-culture studies using T cells and macrophages from WT or IFN-γ KO mice demonstrated that T cells were primary source for IFN-γ production. Co-culture of WT macrophages with WT T cells, but not with IFN-γ-knockout T cells, increased IFN-γ production (p<0.01). Moreover, IFN-γ produced by T cells amplified MCP-1 expression in macrophages and stimulated macrophage migration. Reciprocal interaction between macrophages and T cells in heart stimulates IFN-γ 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.Keywords
This publication has 45 references indexed in Scilit:
- Outer Membrane Protein A (OmpA) of Shigella flexneri 2a Links Innate and Adaptive Immunity in a TLR2-dependent Manner and Involvement of IL-12 and Nitric OxideJournal of Biological Chemistry, 2012
- Proinflammatory Protein CARD9 Is Essential for Infiltration of Monocytic Fibroblast Precursors and Cardiac Fibrosis Caused by Angiotensin II InfusionAmerican Journal of Hypertension, 2011
- Inhibition and Genetic Ablation of the B7/CD28 T-Cell Costimulation Axis Prevents Experimental HypertensionCirculation, 2010
- Interleukin 6 Knockout Prevents Angiotensin II HypertensionHypertension, 2010
- Monocytic fibroblast precursors mediate fibrosis in angiotensin-II-induced cardiac hypertrophyJournal of Molecular and Cellular Cardiology, 2010
- The role of aldosterone in mediating the dependence of angiotensin hypertension on IL-6American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2009
- Cross-regulation of Signaling Pathways by Interferon-γ: Implications for Immune Responses and Autoimmune DiseasesImmunity, 2009
- Gamma Interferon Signaling in Macrophage Lineage Cells Regulates Central Nervous System Inflammation and Chemokine ProductionJournal of Virology, 2009
- Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunctionThe Journal of Experimental Medicine, 2007
- T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-γ and IL-13 productionProceedings of the National Academy of Sciences of the United States of America, 2007