title: Hypoxia induces intercellular adhesion molecule-1 on cultured human tubular cells.
abstract: The adverse effects of acute renal ischemia are partly mediated through an infiltration of inflammatory cells into the tubulointerstitium. The expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) by resident renal cells (endothelial cells and tubular cells) may facilitate this process. We investigated whether hypoxia stimulates the expression of ICAM-1 by cultured human proximal tubular cells (HPTC). Hypoxic culture conditions (PO2 < 4 kPa) stimulated the expression of ICAM-1 by HPTC in a time-dependent manner (P < 0.0001) as demonstrated by quantitative flow cytometry analysis. Quantitative PCR demonstrated an increase in ICAM-1 transcription. Re-oxygenation of tubular cells did not increase ICAM-1 expression further. TNF alpha concentration in culture supernatants increased with hypoxia, but blocking experiments demonstrated that TNF alpha was not implicated in hypoxia-induced expression of ICAM-1. Furthermore, the cytokines IL-6 and IL-1 beta were not involved, but the effect of hypoxia was blocked by PDTC, an antioxidant that may inhibit the activation of the transcription factor NF-kappa B. These data demonstrate that hypoxia is a stimulus that induces the synthesis and expression of the adhesion molecule ICAM-1, presumably via the activation of NF-kappa B.
authors.affiliation: Department of Nephrology, Leicester General Hospital, England, United Kingdom. christian.combe@nephro.h.bordeaux2.fr
authors.forename: C
authors.initials: C
authors.lastname: Combe
authors.forename: C J
authors.initials: CJ
authors.lastname: Burton
authors.forename: P
authors.initials: P
authors.lastname: Dufourco
authors.forename: S
authors.initials: S
authors.lastname: Weston
authors.forename: T
authors.initials: T
authors.lastname: Horsburgh
authors.forename: J
authors.initials: J
authors.lastname: Walls
authors.forename: K P
authors.initials: KP
authors.lastname: Harris
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016207:Cytokines; D013859:Thiocarbamates; D018799:Intercellular Adhesion Molecule-1; C066229:prolinedithiocarbamate; D011392:Proline; D010100:Oxygen