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Tumor Necrosis Factor‐alpha mediates cardiac mast cell regulation of fibroblast function
Author(s) -
McLarty Jennifer L.,
Carver Wayne E.,
Brower Gregory L.,
Janicki Joseph S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a591-b
Subject(s) - fibroblast , mast cell , extracellular matrix , tumor necrosis factor alpha , microbiology and biotechnology , contraction (grammar) , chemistry , biology , in vitro , endocrinology , immunology , biochemistry
We and others have previously demonstrated that mast cells are involved in pathologic remodeling of the myocardium. Specifically, mast cells cause degradation of the extracellular matrix and modify expression of collagen, matrix metalloproteases, and integrin receptors in cardiac fibroblasts. However, the mechanism by which mast cells induce these functional changes in fibroblast phenotype has not been established. Cardiac mast cells are known to contain tumor necrosis factor‐α (TNF‐α). Therefore, a potential mechanism eliciting these responses in fibroblasts is TNF‐α signaling. The present study was carried out to determine the effects of TNF‐α on fibroblast‐mediated collagen gel contraction. Accordingly, primary adult cardiac fibroblast cultures were incubated with varying concentrations of TNF‐α to determine the effect on contraction of 3‐D collagen gels. Fibroblasts were also incubated with cardiac mast cell supernatants and their ability to contract collagen gels was measured. Consistent with our previous findings, fibroblast contraction of collagen gels was inhibited by mast cell supernatant. Incubation with TNF‐α produced a concentration dependent inhibition of collagen gel contraction. These findings demonstrate that modulation of the cardiac fibroblasts response by mast cells is at least partly mediated by their release of TNF‐α.