title: Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages.
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.
  
  
  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.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kumada
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagaretani
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Azumi
authors.initials: A
authors.lastname: Nagasawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D052242:Adiponectin; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D002478:Cells, Cultured / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D019899:Paracrine Communication; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D016753:Interleukin-10; D020780:Matrix Metalloproteinase 9