PMID- 19617629 OWN - NLM STAT- MEDLINE DCOM- 20091019 LR - 20211020 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 284 IP - 38 DP - 2009 Sep 18 TI - Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. PG - 25569-75 LID - 10.1074/jbc.M109.019786 [doi] AB - Macrophages participate pivotally in the pathogenesis of many chronic inflammatory diseases including atherosclerosis. Adiponectin, a vasculoprotective molecule with insulin-sensitizing and anti-atherogenic properties, suppresses pro-inflammatory gene expression in macrophages by mechanisms that remain incompletely understood. This study investigated the effects of adiponectin on major pro-inflammatory signaling pathways in human macrophages. We demonstrate that pretreatment of these cells with adiponectin inhibits phosphorylation of nuclear factor kappaB inhibitor (IkappaB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), induced by either lipopolysaccharide (LPS) or tumor necrosis factor (TNF) alpha, as well as STAT3 phosphorylation induced by interleukin-6 (IL6). Antagonism of IL10 by either neutralizing antibodies or siRNA-mediated silencing did not abrogate the anti-inflammatory actions of adiponectin, indicating that the ability of adiponectin to render human macrophages tolerant to various pro-inflammatory stimuli does not require this cytokine. A systematic search for adiponectin-inducible genes with established anti-inflammatory properties revealed that adiponectin augmented the expression of A20, suppressor of cytokine signaling (SOCS) 3, B-cell CLL/lymphoma (BCL) 3, TNF receptor-associated factor (TRAF) 1, and TNFAIP3-interacting protein (TNIP) 3. These results suggest that adiponectin triggers a multifaceted response in human macrophages by inducing the expression of various anti-inflammatory proteins that act at different levels in concert to suppress macrophage activation. FAU - Folco, Eduardo J AU - Folco EJ AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Rocha, Viviane Z AU - Rocha VZ FAU - Lopez-Ilasaca, Marco AU - Lopez-Ilasaca M FAU - Libby, Peter AU - Libby P LA - eng GR - R01 HL034636/HL/NHLBI NIH HHS/United States GR - R01-HL0831554/HL/NHLBI NIH HHS/United States GR - R01-HL034636/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090718 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (ADIPOQ protein, human) RN - 0 (Adiponectin) RN - 0 (B-Cell Lymphoma 3 Protein) RN - 0 (BCL3 protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (I-kappa B Proteins) RN - 0 (IL10 protein, human) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-6) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (Nuclear Proteins) RN - 0 (Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (TNF Receptor-Associated Factor 1) RN - 0 (TNIP3 protein, human) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.19.12 (TNFAIP3 protein, human) RN - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3) SB - IM MH - Adiponectin/metabolism/pharmacology MH - B-Cell Lymphoma 3 Protein MH - Cell Line MH - DNA-Binding Proteins MH - Gene Expression Regulation/drug effects MH - Humans MH - I-kappa B Proteins/metabolism MH - Inflammation/metabolism MH - Interleukin-10/metabolism/*pharmacology MH - Interleukin-6/metabolism/pharmacology MH - Intracellular Signaling Peptides and Proteins MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Lipopolysaccharides/pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Macrophages/*metabolism MH - Nuclear Proteins/biosynthesis MH - Phosphorylation/drug effects MH - Proteins/metabolism MH - Proto-Oncogene Proteins/biosynthesis MH - STAT3 Transcription Factor/biosynthesis MH - TNF Receptor-Associated Factor 1/biosynthesis MH - Transcription Factors/biosynthesis MH - Tumor Necrosis Factor alpha-Induced Protein 3 MH - Tumor Necrosis Factor-alpha/metabolism/pharmacology MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC2757958 EDAT- 2009/07/21 09:00 MHDA- 2009/10/20 06:00 PMCR- 2010/09/18 CRDT- 2009/07/21 09:00 PHST- 2009/07/21 09:00 [entrez] PHST- 2009/07/21 09:00 [pubmed] PHST- 2009/10/20 06:00 [medline] PHST- 2010/09/18 00:00 [pmc-release] AID - S0021-9258(18)81031-6 [pii] AID - M109.019786 [pii] AID - 10.1074/jbc.M109.019786 [doi] PST - ppublish SO - J Biol Chem. 2009 Sep 18;284(38):25569-75. doi: 10.1074/jbc.M109.019786. Epub 2009 Jul 18.