Vitamin D limits chemokine expression in adipocytes and macrophage migration in vitro and in male mice.
Vitamin D (VD) displays immunoregulatory effects and reduces adipocyte inflammation, which may participate to a reduction of adipose tissue macrophage infiltration in the context of obesity-associated low-grade inflammation. These observations have been described mainly in vitro, through the evaluation of a limited number of inflammatory markers. Here, we studied the effects of 1,25 dihydroxy-VD on chemokine network expression in adipocytes (by transcriptomic approach), and we confirm the physiological relevance of these data in vivo, by demonstrating the effect of VD on cytokine and chemokine gene expression as well as on macrophage infiltration in adipose tissue. 1,25 dihydroxy-VD down-regulated (-1.3- to -10.8-fold) the mRNA expression of 29 chemokines and limited macrophage migration in TNFα-conditioned adipocyte medium (1.5-fold; P < .05). This effect was associated with a reduction in p65 and IκB (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) phosphorylation (2-fold compared with TNFα; P < .05). The effects of VD were confirmed in mice injected ip with lipopolysaccharide (acute inflammation) and diet-induced obese mice (metabolic inflammation), where the levels of mRNA encoding proinflammatory cytokines and chemokines (∼2-fold) were reduced in adipocytes (acute and metabolic inflammation) and adipose tissue and that macrophage infiltration was also inhibited in the adipose tissue of obese mice (metabolic inflammation). Altogether, these results showed that VD displayed a global immunoregulatory impact on adipocytes, notably via the inhibition of chemokine expression and macrophage infiltration in inflamed adipose tissue.
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1260; Inserm, Unité Mixte de Recherche 1062, Nutrition, Obésité et Risque Thrombotique; and Faculté de Médecine, Aix-Marseille Université, F-13385 Marseille Cedex 05, France.
Esma
E
Karkeni
Julie
J
Marcotorchino
Franck
F
Tourniaire
Julien
J
Astier
Franck
F
Peiretti
Patrice
P
Darmon
Jean-François
JF
Landrier
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D054442:Cell Migration Assays, Macrophage; D002465:Cell Movement / Q000187:drug effects*; D018925:Chemokines / Q000187:drug effects* / Q000235:genetics; D002762:Cholecalciferol / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; D002762:Cholecalciferol; C097949:1,25-dihydroxyvitamin D