Visfatin, an adipocytokine with proinflammatory and immunomodulating properties.
Adipocytokines are mainly adipocyte-derived cytokines regulating metabolism and as such are key regulators of insulin resistance. Some adipocytokines such as adiponectin and leptin affect immune and inflammatory functions. Visfatin (pre-B cell colony-enhancing factor) has recently been identified as a new adipocytokine affecting insulin resistance by binding to the insulin receptor. In this study, we show that recombinant visfatin activates human leukocytes and induces cytokine production. In CD14(+) monocytes, visfatin induces the production of IL-1beta, TNF-alpha, and especially IL-6. Moreover, it increases the surface expression of costimulatory molecules CD54, CD40, and CD80. Visfatin-stimulated monocytes show augmented FITC-dextran uptake and an enhanced capacity to induce alloproliferative responses in human lymphocytes. Visfatin-induced effects involve p38 as well as MEK1 pathways as determined by inhibition with MAPK inhibitors and we observed activation of NF-kappaB. In vivo, visfatin induces circulating IL-6 in BALB/c mice. In patients with inflammatory bowel disease, plasma levels of visfatin are elevated and its mRNA expression is significantly increased in colonic tissue of Crohn's and ulcerative colitis patients compared with healthy controls. Macrophages, dendritic cells, and colonic epithelial cells might be additional sources of visfatin as determined by confocal microscopy. Visfatin can be considered a new proinflammatory adipocytokine.
Moschen
Alexander R
AR
Department of Medicine, Christian Doppler Research Laboratory for Gut Inflammation and Clinical Division of Gastroenterology and Hepatology, Innsbruck Medical University, Innsbruck, Austria.
Kaser
Arthur
A
Enrich
Barbara
B
Mosheimer
Birgit
B
Theurl
Milan
M
Niederegger
Harald
H
Tilg
Herbert
H
D017667:Adipocytes; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase; D012333:RNA, Messenger / Q000097:blood; D011994:Recombinant Proteins; D015398:Signal Transduction
D016207:Cytokines; D007155:Immunologic Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human