Hypoxia-mediated induction of endothelial cell interleukin-1α. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface

R. Shreeniwas, S. Koga, M. Karakurum, D. Pinsky, E. Kaiser, J. Brett, B. A. Wolitzky, C. Norton, J. Plocinski, W. Benjamin, D. K. Burns, A. Goldstein, David Stern

Research output: Contribution to journalArticle

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Abstract

Tissue injury that accompanies hypoxemia/reoxygenation shares features with the host response in inflammation, suggesting that cytokines, such as IL-1, may act as mediators in this setting. Human endothelial cells (ECs) subjected to hypoxia (PO2 ≃ 12-14 Torr) elaborated IL-1 activity into conditioned media in a time-dependent manner; this activity was completely neutralized by an antibody to IL-1α. Production of IL-1 activity by hypoxic ECs was associated with an increase in the level of mRNA for IL-1α, and was followed by induction of endothelial-leukocyte adhesion molecule-1 and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) during reoxygenation. During reoxygenation there was a three- to five-fold increased adherence of leukocytes, partly blocked by antibodies to endothelial- leukocyte adhesion molecule-1 and ICAM-1. Suppressing endothelial-derived IL- 1, using either antibodies to IL-1α, specific antisense oligonucleotides or the IL-1 receptor antagonist, decreased leukocyte adherence to reoxygenated ECs, emphasizing the integral role of IL-1 in the adherence phenomenon. Mice subjected to hypoxia (PO2 ≃ 30-40 Torr) displayed increased plasma levels of IL-1α, induction of IL-1α mRNA in the lung, and enhanced expression of ICAM-1 in pulmonary tissue compared with normoxic controls. These data suggest that hypoxia is a stimulus which induces EC synthesis and release of IL-1α, resulting in an autocrine enhancement in the expression of adhesion molecules.

Original languageEnglish (US)
Pages (from-to)2333-2339
Number of pages7
JournalJournal of Clinical Investigation
Volume90
Issue number6
DOIs
StatePublished - Jan 1 1992

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Cell Adhesion Molecules
Interleukin-1
Endothelial Cells
Intercellular Adhesion Molecule-1
E-Selectin
Antibodies
Leukocytes
Hypoxia
Lung
Messenger RNA
Interleukin-1 Receptors
Antisense Oligonucleotides
Conditioned Culture Medium
Cytokines
Inflammation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Hypoxia-mediated induction of endothelial cell interleukin-1α. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface. / Shreeniwas, R.; Koga, S.; Karakurum, M.; Pinsky, D.; Kaiser, E.; Brett, J.; Wolitzky, B. A.; Norton, C.; Plocinski, J.; Benjamin, W.; Burns, D. K.; Goldstein, A.; Stern, David.

In: Journal of Clinical Investigation, Vol. 90, No. 6, 01.01.1992, p. 2333-2339.

Research output: Contribution to journalArticle

Shreeniwas, R, Koga, S, Karakurum, M, Pinsky, D, Kaiser, E, Brett, J, Wolitzky, BA, Norton, C, Plocinski, J, Benjamin, W, Burns, DK, Goldstein, A & Stern, D 1992, 'Hypoxia-mediated induction of endothelial cell interleukin-1α. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface', Journal of Clinical Investigation, vol. 90, no. 6, pp. 2333-2339. https://doi.org/10.1172/JCI116122
Shreeniwas, R. ; Koga, S. ; Karakurum, M. ; Pinsky, D. ; Kaiser, E. ; Brett, J. ; Wolitzky, B. A. ; Norton, C. ; Plocinski, J. ; Benjamin, W. ; Burns, D. K. ; Goldstein, A. ; Stern, David. / Hypoxia-mediated induction of endothelial cell interleukin-1α. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 6. pp. 2333-2339.
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