title: Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells.
abstract: During acute inflammation, P-selectin is transiently mobilized from Weibel-Palade bodies to the surface of histamine-activated endothelial cells, where it mediates rolling adhesion of neutrophils under hydrodynamic flow. During chronic or allergic inflammation, sustained expression of P-selectin on the endothelial cell surface has been observed. We found that the cytokines interleukin 4 (IL-4) or oncostatin M (OSM) induced a five- to ninefold increase in P-selectin messenger RNA (mRNA) in human umbilical vein endothelial cells (HUVEC) that persisted as long as 72 h. IL-4 elevated P-selectin mRNA by increasing its transcription rate rather than by prolonging its already long half-life. Stimulation of P-selectin transcription by IL-4 or OSM required new protein synthesis and tyrosine phosphorylation of cellular proteins. Tumor necrosis factor alpha, IL-1 beta, lipopolysaccharide, or IL-3 did not increase P-selectin mRNA in HUVEC, and did not augment the IL-4-induced increase in P-selectin transcripts. IL-4 or OSM increased P-selectin protein on the cell surface as well as in Weibel-Palade bodies. Under flow conditions, neutrophils rolled on P-selectin expressed by IL-4-treated HUVEC, and even more neutrophils rolled on P-selectin after IL-4-treated HUVEC were stimulated with histamine. These data demonstrate that IL-4 or OSM stimulates endothelial cells to synthesize more P-selectin over prolonged periods. The increased expression of P-selectin may facilitate the emigration of leukocytes into sites of chronic or allergic inflammation.
authors.affiliation: W.K. Warren Medical Research Institute, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yao
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: H
authors.initials: H
authors.lastname: Setiadi
authors.forename: K D
authors.initials: KD
authors.lastname: Patel
authors.forename: R P
authors.initials: RP
authors.lastname: McEver
mesh_terms: D000818:Animals; D016227:Benzoquinones; D002448:Cell Adhesion; D002478:Cells, Cultured; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D019833:Genistein; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009504:Neutrophils / Q000166:cytology; D053683:Oncostatin M; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D016227:Benzoquinones; D019040:E-Selectin; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007377:Interleukin-3; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; C508351:OSM protein, human; C508352:Osm protein, mouse; D019007:P-Selectin; D010455:Peptides; D011809:Quinones; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D053683:Oncostatin M; D017828:Rifabutin; D015847:Interleukin-4; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases