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Biochem Biophys Res Commun. 2007 Oct 12;362(1):200-205. doi: 10.1016/j.bbrc.2007.08.003. Epub 2007 Aug 9.

Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts.

Author information

1
Division of Cardiology, University of Colorado at Denver and Health Sciences Center, and Denver Health Medical Center, B-139, 4200 E. 9th Avenue, Denver, CO 80262, USA. Electronic address: Dale.Brown@uchsc.edu.
2
Division of Cardiology, University of Colorado at Denver and Health Sciences Center, and Denver Health Medical Center, B-139, 4200 E. 9th Avenue, Denver, CO 80262, USA.

Abstract

We sought to define the relationship between cytokine stimulated release of matrix metalloproteinases (MMPs) and cell migration using adult rat cardiac fibroblasts. Interleukin-1beta (IL-1beta) increased release of MMP-2, -3, and -9, and TIMP-1, by 3-6-fold, measured by immunoblotting and gel zymography. Tumor necrosis factor-alpha (TNFalpha) augmented IL-1beta stimulated release of MMP-9, but not MMP-2 or -3. Transforming growth factor-beta1 (TGFbeta1) attenuated all the responses to IL-1beta. IL-1beta was also the most robust stimulus of adult rat cardiac fibroblast migration, measured in Boyden chamber assays. The combination of IL-1beta plus TNFalpha substantially enhanced migration, whereas TGFbeta1 strongly inhibited the migratory response to IL-1beta. The pan-selective MMP inhibitor GM 6001 effectively blocked IL-1beta stimulated migration. Pharmacologic inhibitors selective for ERK, JNK, and p38 MAP kinase pathways inhibited the IL-1beta regulation of individual MMPs. Increased MMP activity associated with migration of cardiac fibroblasts may be important determinants of cytokine-directed remodeling of injured myocardium.

PMID:
17706606
PMCID:
PMC2017114
DOI:
10.1016/j.bbrc.2007.08.003
[Indexed for MEDLINE]
Free PMC Article

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