title: Regulation of the expression of intercellular adhesion molecule 1 in cultured human endothelial cells derived from rheumatoid synovium.
abstract: OBJECTIVE
  To examine the regulation of intercellular adhesion molecule 1 (ICAM-1) in human synovial microvascular endothelial cells (HSE) and human umbilical vein endothelial cells (HUVE) upon exposure to a variety of agents.
  
  
  METHODS
  Cultured endothelial cells were treated with various cytokines alone and in combination. The expression of ICAM-1 was evaluated at several levels, including an investigation of messenger RNA (mRNA) and surface protein expression.
  
  
  RESULTS
  Treatment of HSE with interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor alpha (TNF alpha) resulted in minimal increases in ICAM-1 expression, in contrast to findings with HUVE. Incubation of HUVE or HSE with IL-1 or TNF in combination with interferon-gamma (IFN gamma) greatly potentiated the increase in ICAM-1 surface expression. The synergistic effect of IFN gamma and TNF was confirmed by several methods, including a cell-based enzyme-linked immunosorbent assay, fluorescence-activated cell sorting, immunofluorescence staining, and determination of mRNA levels. IFN gamma also augmented the actions of several other agonists on HSE, i.e., IL-4, lipopolysaccharide, and TNF beta/lymphotoxin. Immunoprecipitation of TNF alpha + IFN gamma-stimulated, 125I-labeled HSE cells with anti-ICAM-1 revealed a single 90-kd band, similar in size to ICAM-1 from HUVE treated in an identical manner. Unexpectedly, IFN gamma alone was a potent stimulus for HSE ICAM-1 mRNA synthesis, but was relatively ineffective in HUVE.
  
  
  CONCLUSIONS
  These studies indicate that IFN gamma plays a critical synergistic role in the regulation of ICAM-1 expression in human synovial endothelial cells.
authors.affiliation: Institute for Inflammation and Autoimmunity, Miles Inc., West Haven, CT 06516.
authors.forename: M E
authors.initials: ME
authors.lastname: Gerritsen
authors.forename: K A
authors.initials: KA
authors.lastname: Kelley
authors.forename: G
authors.initials: G
authors.lastname: Ligon
authors.forename: C A
authors.initials: CA
authors.lastname: Perry
authors.forename: C P
authors.initials: CP
authors.lastname: Shen
authors.forename: A
authors.initials: A
authors.lastname: Szczepanski
authors.forename: W W
authors.initials: WW
authors.lastname: Carley
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008875:Middle Aged; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1