Adiponectin stimulates release of CCL2,-3,-4 and-5 while the surface abundance of CCR2 and-5 is simultaneously reduced in primary human monocytes

Neumeier, Markus and Bauer, Sabrina and Bruehl, Hilke and Eisinger, Kristina and Kopp, Andrea and Abke, Sabine and Walter, Roland and Schaeffler, Andreas and Buechler, Christa (2011) Adiponectin stimulates release of CCL2,-3,-4 and-5 while the surface abundance of CCR2 and-5 is simultaneously reduced in primary human monocytes. CYTOKINE, 56 (3). pp. 573-580. ISSN 1043-4666,

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Abstract

The adipokine adiponectin is well known to affect the function of immune cells and upregulation of CCL2 by adiponectin in monocytes/macrophages has already been reported. In the current study the effect of adiponectin on CCL2, -3, -4, and -5 and their corresponding receptors CCR1, CCR2, and CCR5 has been analyzed. Adiponectin elevates mRNA and protein of the CC chemokines in primary human monocytes. Simultaneously the surface abundance of CCR2 and CCR5 is reduced while CCR1 is not affected. Downregulation of CCR2 by adiponectin is blocked by a CCR2 antagonist although expression of the CCL2 regulated genes CCR2 and TGF-beta 1 is not altered in the adiponectin-incubated monocytes. CCL2, -3, and -5 concentrations measured in supernatants of monocytes of normal-weight (NW), overweight (OW), and type 2 diabetic (T2D) patients positively correlate with BMI and are increased in obesity and T2D. In contrast CCL4 is similarly abundant in the supernatants of all of these monocytes. The degree of adiponectin-mediated induction of the chemokines CCL3, -4, and -5 negatively correlates with their basal levels and upregulation of CCL3 and CCL5 is significantly impaired in OW and T2D cells. Serum concentrations of these chemokines are almost equal in the three groups and do not correlate with the levels in monocyte supernatants. In conclusion these data demonstrate that adiponectin stimulates release of CCL2 to CCL5 in primary human monocytes, and induction in cells of overweight probands is partly impaired. Adiponectin also lowers surface abundance of CCR2 and CCR5 and downregulation of CCR2 seems to depend on autocrine/paracrine effects of CCL2. (C) 2011 Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: CHEMOATTRACTANT PROTEIN-1; INSULIN-RESISTANCE; CHEMOKINE RECEPTORS; ADIPOSE-TISSUE; HEPATIC STEATOSIS; EXPRESSION; MICE; DISEASE; MECHANISMS; INHIBITION; CC-chemokines; CC-chemokine receptors; Obesity
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 May 2020 05:42
Last Modified: 26 May 2020 05:42
URI: https://pred.uni-regensburg.de/id/eprint/19707

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