β3-Adrenergic Receptor Stimulation Induces E-Selectin-mediated Adipose Tissue Inflammation
| Autor: | Kimberly A. Negrin, Anouch Matevossian, Marina T. Paul, Rachel J. Roth Flach, Thomas E. Akie, Michael P. Czech |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Neutrophils Lipolysis Leukocyte adhesion molecule Adipose tissue macrophages Interleukin-1beta Adipose tissue Inflammation Biochemistry Mice Internal medicine E-selectin Human Umbilical Vein Endothelial Cells medicine Animals Humans Molecular Biology Chemokine CCL2 Mice Knockout biology Tumor Necrosis Factor-alpha 3T3-L1 Cell Biology Mice Inbred C57BL Metabolism Endocrinology Adipose Tissue Diabetes Mellitus Type 2 Immune System Receptors Adrenergic beta-3 biology.protein medicine.symptom E-Selectin Wound healing |
| Zdroj: | Journal of Biological Chemistry. 288:2882-2892 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m112.412346 |
| Popis: | 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 β3-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 β3-adrenergic stimulation acts through up-regulation of E-selectin in adipose tissue endothelial cells to induce neutrophil infiltration. Background: Studies suggest that lipolysis induces adipose tissue inflammation, commonly associated with type 2 diabetes. Results: Activation of adipose-resident endothelium is required for β3-adrenergic receptor-mediated but not fasting-induced inflammation. Conclusion: Both β3-adrenergic receptor stimulation and fasting induce adipose tissue inflammation, but by different mechanisms. Significance: The study shows heterogeneity of immune cell dynamics in adipose tissue. |
| Databáze: | OpenAIRE |
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