|Smith, C Wayne|
Submitted to: American Journal of Physiology - Cell Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2006
Publication Date: 2/1/2006
Citation: Lafontant, P.J., Burns, A.R., Donnachie, E., Haudek, S.B., Smith, C.W., Entman, M.L. 2006. Oncostatin M differentially regulates CXC chemokines in mouse cardiac fibroblasts. American Journal of Physiology - Cell Physiology. 291:C18-C26. Interpretive Summary: The consequences of myocardial infarction are both benefited and exaggerated by opening up the coronary arteries to allow blood flow to return to ischemic tissue. The return of blood flow causes inflammation with white blood cells entering the tissue. These cells have the ability to further damage the tissue and to promote healing. This paper deals with a growth factor that is released by the white blood cells and its effect on fibroblasts, the cells that are necessary for tissue repairs after injury. This growth factor is called oncostatin M (OSM) and in this paper is shown for the first time to have the ability to stimulate cardiac fibroblasts to synthesize proteins that are known to promote new blood vessel growth. These results provide information that has potential bearing on the treatment of one of the complications of obesity and atherosclerosis, myocardial ischemia.
Technical Abstract: Ischemia-reperfusion injury in the heart is characterized by marked infiltration of neutrophils in the myocardial interstitial space. Studies in human, canine, and murine models have revealed oncostatin M (OSM) expression in infiltrating leukocytes. In an effort to assess possible roles of OSM in the myocardium, we used cardiac fibroblasts (mCFs) isolated from adult mouse heart to determine whether recombinant murine OSM regulates the synthesis and release of MIP2/CXCL2, KC/CXCL1, and LIX/CXCL5, which are three potent neutrophil chemoattractants in the mouse. Our results demonstrate that mCFs express OSM receptors and that, within the IL-6 cytokine family, OSM uniquely induces significant release of KC and LIX in mCFs. In addition, although OSM activates the JAK-signal transducers and activators of transcription and MAPK pathways, we demonstrate that the OSM-mediated CXC chemokine release in mCFs is also dependent on the activation of the phosphatidylinositol 3-kinase pathway.