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Hypoxic induction of interleukin-8 gene expression in human endothelial cells.
Karakurum, M. Shreeniwas, R. Chen, Jing Xian Pinsky, David J. Yan, Shirley ShiDu Anderson, M. Sunouchi, K. Major, J. Hamilton, T. Kuwabara, Keisuke
Karakurum, M.
Shreeniwas, R.
Chen, Jing Xian
Pinsky, David J.
Yan, Shirley ShiDu
Anderson, M.
Sunouchi, K.
Major, J.
Hamilton, T.
Kuwabara, Keisuke
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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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This is the published version. Copyright 1994 American Society for Clinical Investigation.
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1994-04-01
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American Society for Clinical Investigation
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Karakurum, M., R. Shreeniwas, J. Chen, D. Pinsky, S. D. Yan, M. Anderson, K. Sunouchi, J. Major, T. Hamilton, and K. Kuwabara. "Hypoxic Induction of Interleukin-8 Gene Expression in Human Endothelial Cells." Journal of Clinical Investigation J. Clin. Invest. 93.4 (1994): 1564-570. http://dx.doi.org/10.1172/JCI117135.