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PMID: 17706606 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts.

Biochemical and biophysical research communications ·Vol. 362 ·No. 1 ·2007-10-12 ·Pages 200-205

Brown RD, Jones GM, Laird RE, Hudson P, Long CS

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.

MeSH Terms
Animals Blotting, Western Cell Movement Cytokines/metabolism Fibroblasts/cytology Gene Expression Regulation Heart/physiology Interleukin-1beta/metabolism MAP Kinase Signaling System Matrix Metalloproteinases/metabolism Myocardium/metabolism,pathology Rats Rats, Sprague-Dawley Transforming Growth Factor beta1/metabolism p38 Mitogen-Activated Protein Kinases/metabolism
Chemicals
Cytokines Interleukin-1beta Transforming Growth Factor beta1 p38 Mitogen-Activated Protein Kinases Matrix Metalloproteinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Brown R Dale
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: [email protected].
Jones Gayle M
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.
Laird Rebecca E
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.
Hudson Paul
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.
Long Carlin S
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.
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Article Info
Journal
Biochemical and biophysical research communications
Abbr.
Biochem Biophys Res Commun
ISSN
0006-291X
DOI
10.1016/j.bbrc.2007.08.003
Email
[email protected]
Published
2007-10-12
Epub
2007-00-09
Pages
200-205
Language
English
Region
United States
NLM ID
0372516
PMCID
PMC2017114
Subset
IM
Grants
NHLBI NIH HHS · U01 HL079160 · United States
NHLBI NIH HHS · U01 HL079160-03 · United States
NIGMS NIH HHS · GM 59428 · United States
NHLBI NIH HHS · HL79160 · United States
External Links
PubMed source DOI: 10.1016/j.bbrc.2007.08.003 PMC Full Text View journal details
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