title: Adiponectin stimulates release of CCL2, -3, -4 and -5 while the surface abundance of CCR2 and -5 is simultaneously reduced in primary human monocytes.
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.
authors: Department of Internal Medicine I, Regensburg University Hospital, D-93042 Regensburg, Germany.
authors: Markus
authors: M
authors: Neumeier
authors: Sabrina
authors: S
authors: Bauer
authors: Hilke
authors: H
authors: Brühl
authors: Kristina
authors: K
authors: Eisinger
authors: Andrea
authors: A
authors: Kopp
authors: Sabine
authors: S
authors: Abke
authors: Roland
authors: R
authors: Walter
authors: Andreas
authors: A
authors: Schäffler
authors: Christa
authors: C
authors: Buechler
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D054405:Chemokine CCL3 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D054407:Chemokine CCL4 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D019742:Chemokines, CC / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D050177:Overweight / Q000097:blood / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D052242:Adiponectin; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019713:Receptors, CCR5