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Research Article Free access | 10.1172/JCI117135

Hypoxic induction of interleukin-8 gene expression in human endothelial cells.

M Karakurum, R Shreeniwas, J Chen, D Pinsky, S D Yan, M Anderson, K Sunouchi, J Major, T Hamilton, K Kuwabara, A Rot, R Nowygrod, and D Stern

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

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Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

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Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

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Published April 1, 1994 - More info

Published in Volume 93, Issue 4 on July 21, 2021
J Clin Invest. 2021;93(4):1564–1570. https://doi.org/10.1172/JCI117135.
© 1994 The American Society for Clinical Investigation
Published April 1, 1994 - Version history
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Abstract

Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis.

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Version history
  • Version 1 (April 1, 1994): No description
  • Version 2 (July 21, 2021): Added authors A. Rot, R. Nowygrod, and D. Stern to the author list.
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