Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling.
Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling.
复制标题
DOI：
10.1016/j.cardiores.2006.11.028
复制
发表时间：
2007-05
影响因子：
10.8
通讯作者：
P. Zymek;D. Nah;Marcin Bujak;G. Ren;Anna Koerting;T. Leucker;P. Huebener;G. Taffet;M. Entman;N. Frangogiannis
中科院分区：
文献类型：
--
作者：
P. Zymek;D. Nah;Marcin Bujak;G. Ren;Anna Koerting;T. Leucker;P. Huebener;G. Taffet;M. Entman;N. Frangogiannis
Objective: Interleukin-10 (IL-10) exerts potent anti-inflammatory actions and modulates matrix metalloproteinase expression. We hypothesized that endogenous IL-10 may regulate infarct healing and left ventricular remodeling by promoting resolution of the post-infarction inflammatory response and by modulating extracellular matrix metabolism.Methods: IL-10 null and wildtype (WT) mice underwent reperfused infarction protocols. We compared the healing response and remodeling-associated parameters between IL-10 −/− and WT infarcts. In addition, we studied the effects of IL-10 on inflammatory gene synthesis by stimulated murine cardiac fibroblasts.Results: Infarcted IL-10 −/− mice exhibited comparable mortality rates with WT animals. Although IL-10 −/− mice had higher peak tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1/CCL2 mRNA levels in the infarcted heart than WT mice, both groups demonstrated timely repression of pro-inflammatory cytokine and chemokine mRNA synthesis after 24 h of reperfusion and exhibited a similar time course of resolution of the neutrophil infiltrate. IL-10 gene disruption did not alter fibrous tissue deposition and dilative remodeling of the infarcted heart. Pre-incubation with IL-10 did not modulate the pro-inflammatory phenotype of TNF-α-stimulated cardiac fibroblasts, failing to inhibit chemokine mRNA synthesis. In contrast, transforming growth factor (TGF)-β1 pre-incubation suppressed interferon-γ-inducible protein (IP)-10/CXCL10 synthesis by cardiac fibroblasts exposed to TNF-α.Conclusions: IL-10 signaling plays a non-critical role in suppression of inflammatory mediators, resolution of the inflammatory response, and fibrous tissue deposition following myocardial infarction. This may be due to the relative selectivity of IL-10-mediated anti-inflammatory actions, with respect to cell type and stimulus. Resolution of post-infarction inflammation is likely to involve multiple overlapping regulatory mechanisms controlling various pro-inflammatory pathways activated in the infarcted myocardium.
