title: Heat shock inhibits tnf-induced ICAM-1 expression in human endothelial cells via I kappa kinase inhibition.
abstract: The pulmonary vascular endothelium plays a critical role in lung inflammation. As a result of proinflammatory cytokine expression, adhesion molecules are upregulated on the surface of the endothelial cells. Adhesion molecules facilitate recruitment of leukocytes and thus, have been targeted for potential anti-inflammatory strategies. Prior induction of the stress response through thermal stimulation, or heat shock, alters proinflammatory gene expression by attenuating NF-kappaB signaling. As intercellular adhesion molecule-(ICAM) 1 expression is, in part, NF-kappaB-dependent, we hypothesized that heat shock would inhibit ICAM-1 expression. Heat shocking endothelial cells resulted in heat shock protein (HSP) expression as measured by HSP-70 induction, and decreased TNF-alpha-induced ICAM-1 expression in a manner that appeared to be transcriptionally mediated. Following heat shock, decreased TNF-alpha-induced NF-kappaB activation was observed and was associated with preservation of IkappaB-alpha and a decrease in phosphorylated IkappaB-alpha that correlated to inhibition of I kappa kinase (IKK) activity. Interestingly, exposing respiratory epithelial cells to heat shock, which results in NF-kappaB inhibition, did not affect TNF-induced ICAM-1 expression. We conclude that heat shock decreases endothelial cell ICAM-1 expression via inhibition of IKK activity.
authors.affiliation: Division of Pulmonary Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Kohn
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
authors.forename: Khaled
authors.initials: K
authors.lastname: Bshesh
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Niti
authors.initials: N
authors.lastname: Vasi
authors.forename: Alvin
authors.initials: A
authors.lastname: Denenberg
authors.forename: Christopher
authors.initials: C
authors.lastname: Morris
authors.forename: James
authors.initials: J
authors.lastname: Stark
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Shanley
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1