RRC ID 1312
Author Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, Maeda K, Nagaretani H, Kishida K, Maeda N, Nagasawa A, Funahashi T, Matsuzawa Y.
Title Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages.
Journal Circulation
Abstract BACKGROUND:Vascular inflammation and subsequent matrix degradation play an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipose-specific plasma protein, accumulated to the injured artery and attenuated vascular inflammatory response. Clinically, high plasma adiponectin level was associated with low cardiovascular event rate in patients with chronic renal failure. The present study was designed to elucidate the effects of adiponectin on matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in human monocyte-derived macrophages.
METHODS AND RESULTS:Human monocyte-derived macrophages were incubated with the physiological concentrations of human recombinant adiponectin for the time indicated. Adiponectin treatment dose-dependently increased TIMP-1 mRNA levels without affecting MMP-9 mRNA levels. Adiponectin also augmented TIMP-1 secretion into the media, whereas MMP-9 secretion and activity were unchanged. Time course experiments indicated that TIMP-1 mRNA levels started to increase at 24 hours of adiponectin treatment and were significantly elevated at 48 hours. Adiponectin significantly increased interleukin-10 (IL-10) mRNA expression at the transcriptional level within 6 hours and significantly increased IL-10 protein secretion within 24 hours. Cotreatment of adiponectin with anti-IL-10 monoclonal antibody completely abolished adiponectin-induced TIMP-1 mRNA expression.
CONCLUSIONS:Adiponectin selectively increased TIMP-1 expression in human monocyte-derived macrophages through IL-10 induction. This study identified, for the first time, the adiponectin/IL-10 interaction against vascular inflammation.
Volume 109(17)
Pages 2046-9
Published 2004-5-4
DOI 10.1161/01.CIR.0000127953.98131.ED
PII 01.CIR.0000127953.98131.ED
PMID 15096450
MeSH Adiponectin Arteriosclerosis / etiology Arteriosclerosis / prevention & control Cells, Cultured / metabolism Gene Expression Regulation / drug effects* Humans Inflammation Intercellular Signaling Peptides and Proteins* Interleukin-10 / biosynthesis* Interleukin-10 / genetics Macrophages / drug effects* Macrophages / metabolism Matrix Metalloproteinase 9 / biosynthesis Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism Monocytes / cytology Monocytes / drug effects Paracrine Communication Promoter Regions, Genetic Proteins / pharmacology* Proteins / physiology RNA, Messenger / biosynthesis RNA, Messenger / genetics Recombinant Proteins / pharmacology Tissue Inhibitor of Metalloproteinase-1 / biosynthesis* Tissue Inhibitor of Metalloproteinase-1 / genetics Tissue Inhibitor of Metalloproteinase-1 / metabolism Transfection
IF 23.054
Times Cited 324
Human and Animal Cells THP-1