Hypoxia induces intercellular adhesion molecule-1 on cultured human tubular cells.
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.
Combe
C
C
Department of Nephrology, Leicester General Hospital, England, United Kingdom. christian.combe@nephro.h.bordeaux2.fr
Burton
C J
CJ
Dufourco
P
P
Weston
S
S
Horsburgh
T
T
Walls
J
J
Harris
K P
KP
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
D000975:Antioxidants; D016207:Cytokines; D013859:Thiocarbamates; D018799:Intercellular Adhesion Molecule-1; C066229:prolinedithiocarbamate; D011392:Proline; D010100:Oxygen