Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 313-322 |
| Number of pages | 10 |
| Journal | Cardiovascular Research |
| Volume | 74 |
| Issue number | 2 |
| DOIs | |
| State | Published - May 1 2007 |
| Externally published | Yes |
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Keywords
- Cytokines
- Hispathology
- Infarction
- Interleukins
- Remodeling
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling. / Zymek, Pawel; Nah, Deuk Young; Bujak, Marcin; Ren, Guofeng; Koerting, Anna; Leucker, Thorsten; Huebener, Peter; Taffet, George; Entman, Mark; Frangogiannis, Nikolaos G.
In: Cardiovascular Research, Vol. 74, No. 2, 01.05.2007, p. 313-322.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling
AU - Zymek, Pawel
AU - Nah, Deuk Young
AU - Bujak, Marcin
AU - Ren, Guofeng
AU - Koerting, Anna
AU - Leucker, Thorsten
AU - Huebener, Peter
AU - Taffet, George
AU - Entman, Mark
AU - Frangogiannis, Nikolaos G.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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.
AB - 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.
KW - Cytokines
KW - Hispathology
KW - Infarction
KW - Interleukins
KW - Remodeling
UR - http://www.scopus.com/inward/record.url?scp=34047123693&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047123693&partnerID=8YFLogxK
U2 - 10.1016/j.cardiores.2006.11.028
DO - 10.1016/j.cardiores.2006.11.028
M3 - Article
VL - 74
SP - 313
EP - 322
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 2
ER -