title: Induction of CXCR2 receptor by peroxisome proliferator-activated receptor gamma in human macrophages.
abstract: OBJECTIVE
  Macrophages play a central role in the immune response against infectious organisms. Once activated, macrophages secrete proinflammatory cytokines and chemokines. Interleukin (IL)-8 and related CXC chemokines play a role in the recruitment and activation of phagocytes acting through CXCR1 and CXCR2 receptors. The nuclear receptor peroxisome proliferator-activated receptor (PPAR) gamma exerts antiinflammatory properties in macrophages, by inhibiting cytokine and CC chemokine production. In this study, we investigated whether PPAR-gamma also plays a role in the regulation of the CXC chemokine pathway.
  
  
  RESULTS
  Synthetic PPAR-gamma ligands increase CXCR2 but not CXCR1 gene expression in a PPAR-gamma-dependent manner in primary human macrophages in vitro and in atherosclerotic plaques in vivo. The increase of CXCR2 mRNA was paralleled by an increase in membrane protein expression. EMSA, ChIP, and transient transfection assays indicate that PPAR-gamma activates the CXCR2 promoter by binding to a PPAR response element (PPRE). Finally, human macrophages acquire responsiveness to the CXCR2 ligands (IL-8 and Grobeta), as measured by superoxide anion production, after induction of CXCR2 expression by PPAR-gamma ligands.
  
  
  CONCLUSIONS
  Our results provide a novel mechanism via which PPAR-gamma can enhance the immune response in human macrophages.
authors.affiliation: Institut Pasteur de Lille, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Rigamonti
authors.forename: Coralie
authors.initials: C
authors.lastname: Fontaine
authors.forename: Bruno
authors.initials: B
authors.lastname: Lefebvre
authors.forename: Christian
authors.initials: C
authors.lastname: Duhem
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D054426:Chemokine CXCL2 / Q000494:pharmacology; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism
chemical_list: C499706:CXCL2 protein, human; D054426:Chemokine CXCL2; D016209:Interleukin-8; D047495:PPAR gamma; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B; D013481:Superoxides