β3-Adrenergic receptor stimulation induces E-selectin-mediated adipose tissue inflammation.

Autor: Roth Flach RJ; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA., Matevossian A, Akie TE, Negrin KA, Paul MT, Czech MP
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2013 Jan 25; Vol. 288 (4), pp. 2882-92. Date of Electronic Publication: 2012 Dec 12.
DOI: 10.1074/jbc.M112.412346
Abstrakt: Inflammation induced by wound healing or infection activates local vascular endothelial cells to mediate leukocyte rolling, adhesion, and extravasation by up-regulation of leukocyte adhesion molecules such as E-selectin and P-selectin. Obesity-associated adipose tissue inflammation has been suggested to cause insulin resistance, but weight loss and lipolysis also promote adipose tissue immune responses. While leukocyte-endothelial interactions are required for obesity-induced inflammation of adipose tissue, it is not known whether lipolysis-induced inflammation requires activation of endothelial cells. Here, we show that β(3)-adrenergic receptor stimulation by CL 316,243 promotes adipose tissue neutrophil infiltration in wild type and P-selectin-null mice but not in E-selectin-null mice. Increased expression of adipose tissue cytokines IL-1β, CCL2, and TNF-α in response to CL 316,243 administration is also dependent upon E-selectin but not P-selectin. In contrast, fasting increases adipose-resident macrophages but not neutrophils, and does not activate adipose-resident endothelium. Thus, two models of lipolysis-induced inflammation induce distinct immune cell populations within adipose tissue and exhibit distinct dependences on endothelial activation. Importantly, our results indicate that β(3)-adrenergic stimulation acts through up-regulation of E-selectin in adipose tissue endothelial cells to induce neutrophil infiltration.
Databáze: MEDLINE