PloS one, 2012-05, Vol.7 (5), p.e35506
2012
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- Autor(en) / Beteiligte
- Titel
- Reciprocal interaction between macrophages and T cells stimulates IFN-γ and MCP-1 production in Ang II-induced cardiac inflammation and fibrosis
- Ist Teil von
- PloS one, 2012-05, Vol.7 (5), p.e35506
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0035506Titel-ID: cdi_plos_journals_1324605233
- Format
- –
- Schlagworte
- Actin, Angiotensin, Angiotensin II, Angiotensin II - pharmacology, Animals, Biology, Blood pressure, Body Weight - physiology, Cardiac muscle, Cell culture, Cell migration, Chemokine CCL2 - metabolism, Collagen (type I), Cytokines, Disease, Education, Fibroblasts, Fibrosis, Fibrosis - immunology, Fibrosis - metabolism, Flow cytometry, gamma -Interferon, Heart, Heart diseases, Hospitals, Hypertension, Infiltration, Inflammation, Inflammation - chemically induced, Inflammation - metabolism, Inflammatory response, Infusion, Insulin-like growth factors, Interferon, Interferon-gamma - genetics, Interferon-gamma - metabolism, Ischemia, Kidneys, Laboratories, Leukocyte migration, Leukocytes, Low level, Lymphocytes, Lymphocytes T, Macrophages, Medicine, Metastases, Mice, Mice, Knockout, Monocyte chemoattractant protein, Monocyte chemoattractant protein 1, Muscles, Myocardium - immunology, Myocardium - metabolism, Nervous system, Nitric oxide, Proteins, Recruitment, Rodents, Shigella, Smooth muscle, T-Lymphocytes - metabolism, Transcription factors, Tumor necrosis factor- alpha, Tumor necrosis factor-TNF, Tumor necrosis factor-α, White blood cells, γ-Interferon