title: Reciprocal interaction between macrophages and T cells stimulates IFN-γ and MCP-1 production in Ang II-induced cardiac inflammation and fibrosis.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Ya-lei
authors.initials: YL
authors.lastname: Han
authors.forename: Yu-lin
authors.initials: YL
authors.lastname: Li
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Jia
authors.forename: Ji-zhong
authors.initials: JZ
authors.lastname: Cheng
authors.forename: Yong-fen
authors.initials: YF
authors.lastname: Qi
authors.forename: Hong-jia
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism*; D005355:Fibrosis / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D000804:Angiotensin II; D007371:Interferon-gamma