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United States Department of Agriculture

Agricultural Research Service


item Lafontant, Pascal
item Burns, Alan
item Donnachie, Elizabeth
item Ren, Guofeng
item Frangogiannis, Nikolaos
item Smith, Wayne
item Entman, Mark

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 3/3/2004
Publication Date: 3/3/2004
Citation: Lafontant, P.J., Burns, A.R., Donnachie, E., Ren, G., Frangogiannis, N.G., Smith, C.W., Entman, M.L. 2004. Differential regulation of CXC chemokines by Oncostatin M (OSM) in cardiac fibroblasts [abstract]. Journal of Federation of American Societies for Experimental Biology. 18:A951.

Interpretive Summary:

Technical Abstract: OSM is a member of the IL-6 cytokine family and is produced by activated T-cells, monocytes, and neutrophils (PMNs). In an animal model of myocardial ischemia and reperfusion injury, transmigrated PMNs were frequently found in close proximity to peri-venular cardiac fibroblasts (CFs). We sought to determine if OSM release from PMNs induces chemokine production in CFs. Flow cytometry showed that the OSM receptor and gp130 are expressed on mouse CFs and NIH-3T3 cells. Using specific ELISAs, CFs treated with OSM, but not IL-6, LIF, IL-11, or CT-1, release significant amounts of chemokines by 24h. Specifically, OSM induced a dose-dependent release of KC and LPS-induced chemokine (LIX), both potent PMN chemoattractants, but OSM had no effect on MIP-2. RPA analysis revealed OSM induced KC, but not MIP-2 mRNA in a time and dose dependent manner. OSM induced rapid activation of ERK1/2, in addition to STAT-1 and STAT-3. While an inhibitor of the MAPK pathway (PD98059) did not decrease KC and LIX release, LY294002, an inhibitor of PI3-K significantly decreased the release of the two chemokines, and inhibited KC mRNA induction. Collectively, these findings suggest that OSM induces PMN chemokine release from CFs, partly through a pathway involving PI3-K. We suggest that chemokine-induction by PMN-derived OSM may further enhance fibroblast-mediated PMN recruitment in the injured myocardium.

Last Modified: 09/23/2017
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