Location: Children's Nutrition Research CenterTitle: Stanniocalcin-1 regulates endothelial gene expression and modulates trans-endothelial migration of leukocytes Author
|Smith, C. Wayne|
Submitted to: American Journal of Physiology - Renal Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2006
Publication Date: 2/1/2007
Citation: Chakraborty, A., Brooks, H., Zhang, P., Smith, W.C., Mcreynolds, M.R., Hoying, J.B., Bick, R., Truong, L., Poindexter, B., Lan, H., Elbjeirami, W., Sheikh-Hamad, D. 2007. Stanniocalcin-1 regulates endothelial gene expression and modulates trans-endothelial migration of leukocytes. American Journal of Physiology. 292(2):F895-904. Interpretive Summary: This research deals with the mechanisms by which a type of white blood cell called monocyte moves from the blood into tissues during the process of inflammation. This is an important process allowing these cells to enter fat tissues during the development of obesity. This work demonstrates for the first time that a hormone called stanniocalcin modulates this process. Future studies will examine the possible contribution of this hormone to the inflammatory process induced by obesity.
Technical Abstract: The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) inhibits monocyte chemotactic protein-1- and stromal-derived factor-1alpha (SDF-1alpha)-mediated chemotaxis and diminishes chemokinesis in macrophage-like RAW264.7 and U937 cells in a manner that may involve attenuation of the intracellular calcium signal. STC1 is strongly induced in the kidney following obstructive injury. We hypothesized that STC1 may serve to attenuate the influx of inflammatory cells to the site of tissue injury. In this study, we examined the effect of STC1 on the migration of freshly isolated human macrophages, neutrophils, and T and B lymphocytes through quiescent or IL-1beta-treated human umbilical vein endothelial cell (HUVEC) monolayers. STC1 inhibited transmigration of macrophages and T lymphocytes through quiescent or IL-1beta-activated HUVECs but did not attenuate the transmigration of neutrophils and B lymphocytes. STC1 regulates gene expression in cultured endothelial cells and is detected on the apical surface of endothelial cells in vivo. The data suggest that STC1 plays a critical role in transendothelial migration of inflammatory cells and is involved in the regulation of numerous aspects of endothelial function.