File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH 2-terminal kinases and activator protein-1

TitleAdipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH 2-terminal kinases and activator protein-1
Authors
Issue Date2010
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2010, v. 285 n. 14, p. 10273-10280 How to Cite?
AbstractAdipocyte fatty acid-binding protein (A-FABP) has emerged as an important mediator of inflammation in macrophages. Macrophage-selective ablation of A-FABP alone is sufficient to prevent the development of high cholesterol diet-induced atherosclerosis in apoE-deficient mice. However, the precise mechanisms whereby A-FABP modulates inflammation remain elusive. Here, we report that A-FABP forms a finely tuned positive loop between JNK and activator protein-1 (AP-1) to exacerbate lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Real time PCR and luciferase reporter analysis showed that LPS induced A-FABP expression through transcriptional activation. This effect was mediated by JNK, which promoted the recruitment of c-Jun to a highly conserved AP-1 consensus binding motif located within the proximal region of the A-FABP promoter. LPS-induced transactivation of the A-FABP gene was diminished by either pharmacological inhibition of JNK or knocking down c-Jun or by mutating the AP-1 recognition site within the proximal region (-122 to -116 bp) of the A-FABP promoter. Conversely, the LPS-evoked phosphorylation of JNK, activation of AP-1, and production of pro-inflammatory cytokines were markedly attenuated by pharmacological or genetic suppression of A-FABP in macrophages. Furthermore, the LPS-induced elevation in A-FABP expression could also be prevented by the selective A-FABP inhibitor BMS309403. These findings support the notion that pharmacological inhibition of A-FABP represents a valid strategy for treating inflammation-related disorders such as atherosclerosis. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/132182
ISSN
2014 Impact Factor: 4.573
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong Kong
National Natural Science Foundation of ChinaN_HKU 735/08
30831160518
Collaborative Research FundHKU 2/07C
Funding Information:

This work was supported by Research Grants Council of Hong Kong, the National Natural Science Foundation of China Joint Research Scheme (Projects N_HKU 735/08 and 30831160518), and the Collaborative Research Fund (HKU 2/07C) from the Research Grants Council of Hong Kong.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorHui, Xen_HK
dc.contributor.authorLi, Hen_HK
dc.contributor.authorZhou, Zen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorXiao, Yen_HK
dc.contributor.authorWu, Den_HK
dc.contributor.authorDing, Ken_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2011-03-21T08:59:32Z-
dc.date.available2011-03-21T08:59:32Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2010, v. 285 n. 14, p. 10273-10280en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132182-
dc.description.abstractAdipocyte fatty acid-binding protein (A-FABP) has emerged as an important mediator of inflammation in macrophages. Macrophage-selective ablation of A-FABP alone is sufficient to prevent the development of high cholesterol diet-induced atherosclerosis in apoE-deficient mice. However, the precise mechanisms whereby A-FABP modulates inflammation remain elusive. Here, we report that A-FABP forms a finely tuned positive loop between JNK and activator protein-1 (AP-1) to exacerbate lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Real time PCR and luciferase reporter analysis showed that LPS induced A-FABP expression through transcriptional activation. This effect was mediated by JNK, which promoted the recruitment of c-Jun to a highly conserved AP-1 consensus binding motif located within the proximal region of the A-FABP promoter. LPS-induced transactivation of the A-FABP gene was diminished by either pharmacological inhibition of JNK or knocking down c-Jun or by mutating the AP-1 recognition site within the proximal region (-122 to -116 bp) of the A-FABP promoter. Conversely, the LPS-evoked phosphorylation of JNK, activation of AP-1, and production of pro-inflammatory cytokines were markedly attenuated by pharmacological or genetic suppression of A-FABP in macrophages. Furthermore, the LPS-induced elevation in A-FABP expression could also be prevented by the selective A-FABP inhibitor BMS309403. These findings support the notion that pharmacological inhibition of A-FABP represents a valid strategy for treating inflammation-related disorders such as atherosclerosis. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.-
dc.subject.meshFatty Acid-Binding Proteins - physiology-
dc.subject.meshInflammation - immunology - metabolism-
dc.subject.meshJNK Mitogen-Activated Protein Kinases - genetics - metabolism-
dc.subject.meshMacrophages - metabolism-
dc.subject.meshTranscription Factor AP-1 - genetics - metabolism-
dc.titleAdipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH 2-terminal kinases and activator protein-1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=285&issue=14 &spage=10273&epage=10280&date=2010&atitle=Adipocyte+fatty+acid-binding+protein+modulates+inflammatory+responses+in+macrophages+through+a+positive+feedback+loop+involving+c-Jun+NH2-terminal+kinases+and+activator+protein-1-
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M109.097907en_HK
dc.identifier.pmid20145251en_HK
dc.identifier.pmcidPMC2856232-
dc.identifier.scopuseid_2-s2.0-77951232674en_HK
dc.identifier.hkuros178258en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951232674&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume285en_HK
dc.identifier.issue14en_HK
dc.identifier.spage10273en_HK
dc.identifier.epage10280en_HK
dc.identifier.isiWOS:000276264600011-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.relation.projectAdipocyte fatty acid binding protein as a novel diagnostic marker and therapeutic target to combat vascular complications of diabetes: mechanisms and clinical implications-
dc.identifier.scopusauthoridHui, X=26666795900en_HK
dc.identifier.scopusauthoridLi, H=8042135900en_HK
dc.identifier.scopusauthoridZhou, Z=8417885800en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridXiao, Y=36464707600en_HK
dc.identifier.scopusauthoridWu, D=7404297751en_HK
dc.identifier.scopusauthoridDing, K=12243675000en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats