ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P176

Adiponectin stimulates monocytic release of CCL2, -3, -4 and -5 concomitantly reduces the surface abundance of CCR1, -2 and -5

Johanna Weigert, Markus Neumeier, Hilke Brühl, Cornelius Bollheimer, Roland Büttner, Andreas Schäffler, Jürgen Schölmerich & Christa Buechler

Internal Medicine I, Regensburg, Germany.

Background: Systemic adiponectin is reduced in patients with obesity and type 2 diabetes mellitus. Peripheral monocytes of type 2 diabetic patients are activated and show a higher surface abundance of CCR2. Inflammatory markers like CCL2 are elevated in the serum of these patients. Therefore, the influence of adiponectin on the release of CC chemokines and the abundance of the corresponding receptors were investigated in monocytic cells.

Methods: Primary human monocytes were isolated and incubated with recombinant adiponectin (10 μg/ml) for 24 h. GeneChip analysis was performed and ten out of 23 known CC-chemokines were found expressed in human blood monocytes by GeneChip analysis and the mRNA of eight of these chemokines was induced by adiponectin.

Results: Elevated CCL2 to CCL5 mRNA and protein secretion were confirmed by real-time RT-PCR and ELISA, respectively. The p38 MAPK inhibitor SB 203580 abrogated adiponectin-mediated release of CCL2 and CCL3. CCL2 binds to the G-protein coupled receptors CCR2, CCL3 and CCL5 to CCR1 and CCR5, CCL4 and CCL5 to CCR5. The surface abundance of these receptors was significantly reduced in adiponectin treated monocytes. The mRNA expression of CCR1 and CCR2 was not affected whereas CCR5 mRNA was slightly elevated. CCR1 protein was lower in adiponectin-treated monocytes and CCR5 was increased when total cell lysates were investigated by immunoblot. CCL2 had been described to induce the mRNA expression of CCR2 and TGF-beta? in human monocytes. However, the abundance of these mRNAs was not altered in adiponectin-stimulated monocytes arguing against an autocrine or paracrine effects of this chemokine.

Conclusions: Therefore, it is concluded that adiponectin induces the release of CCL2 to CCL5 and simultaneously reduces the surface expression of the corresponding receptors and thereby may prevent an autocrine or paracrine activation of monocytes as has been demonstrated for CCL2 herein.

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