PMID- 16249002 OWN - NLM STAT- MEDLINE DCOM- 20061222 LR - 20171116 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 187 IP - 2 DP - 2006 Aug TI - Pro-atherogenic effect of interleukin-4 in endothelial cells: modulation of oxidative stress, nitric oxide and monocyte chemoattractant protein-1 expression. PG - 285-91 AB - BACKGROUND: Although considered as an anti-inflammatory cytokine, interleukin-4 (IL-4) has been shown to be pro-atherogenic in mice models of atherosclerosis. OBJECTIVES: In order to elucidate this paradox, we have investigated the effects of IL-4 on characteristic atherogenic parameters in human umbilical vein endothelial cells (HUVECs): production of reactive oxygen species, expression of monocyte chemoattractant protein-1 (MCP-1) and nitric oxide (NO) bioavailability. RESULTS: Incubation of HUVECs with IL-4 resulted in an increased production of reactive oxygen species and extracellular O(2)(-)(*) measured using fluorogenic probes and Cytochrome c that was inhibited by superoxide dismutase or gp91ds-tat, a selective NADPH oxidase inhibitor. The latter also inhibited IL-4 induced over-expression of MCP-1 mRNA measured by classical and real time RT-PCR. Incubation of HUVECs with IL-4 reduced thrombin-induced NO release, detected by electrochemistry, an effect which was reversed by incubation with superoxide dismutase. Both production of reactive oxygen species and MCP-1 mRNA over-expression induced by IL-4 were fully inhibited by selective inhibitors of phosphatidyl inositol 3-kinase. CONCLUSION: The data demonstrate that IL-4 up-regulates the expression of MCP-1 and decreases NO bioavailability through activation of NADPH oxidase in endothelial cells. These results are in favor of a pro-inflammatory and pro-atherogenic effect of IL-4 in vascular tissues. FAU - Walch, L AU - Walch L AD - UMR7131 CNRS/Universite Pierre et Marie Curie (Paris 6), Hopital Broussais, 102 rue Didot, 75014 Paris, France. laurence.walch@brs.ap-hop-paris.fr FAU - Massade, L AU - Massade L FAU - Dufilho, M AU - Dufilho M FAU - Brunet, A AU - Brunet A FAU - Rendu, F AU - Rendu F LA - eng PT - Journal Article DEP - 20051024 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Arachidonic Acids) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (IL4 protein, human) RN - 0 (Morpholines) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) RN - 00XIW1CR0F (arachidonyltrifluoromethane) RN - 207137-56-2 (Interleukin-4) RN - 31C4KY9ESH (Nitric Oxide) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.6.3.- (NADPH Oxidases) SB - IM MH - Arachidonic Acids/pharmacology MH - Atherosclerosis/immunology/*metabolism MH - Chemokine CCL2/*genetics/metabolism MH - Chromones/pharmacology MH - Endothelium, Vascular/cytology/drug effects/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Humans MH - Interleukin-4/*metabolism/pharmacology MH - Morpholines/pharmacology MH - NADPH Oxidases/metabolism MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type II/metabolism MH - Oxidative Stress/drug effects/*immunology MH - RNA, Messenger/metabolism MH - Reactive Oxygen Species/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/metabolism/pharmacology MH - Umbilical Veins/cytology EDAT- 2005/10/27 09:00 MHDA- 2006/12/23 09:00 CRDT- 2005/10/27 09:00 PHST- 2005/05/12 00:00 [received] PHST- 2005/08/31 00:00 [revised] PHST- 2005/09/20 00:00 [accepted] PHST- 2005/10/27 09:00 [pubmed] PHST- 2006/12/23 09:00 [medline] PHST- 2005/10/27 09:00 [entrez] AID - S0021-9150(05)00606-4 [pii] AID - 10.1016/j.atherosclerosis.2005.09.016 [doi] PST - ppublish SO - Atherosclerosis. 2006 Aug;187(2):285-91. doi: 10.1016/j.atherosclerosis.2005.09.016. Epub 2005 Oct 24.