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Research Article Free access | 10.1172/JCI115563

Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells.

G P Dupont, T P Huecksteadt, B C Marshall, U S Ryan, J R Michael, and J R Hoidal

Department of Medicine, University of Utah School of Medicine, Salt Lake City.

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Department of Medicine, University of Utah School of Medicine, Salt Lake City.

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Department of Medicine, University of Utah School of Medicine, Salt Lake City.

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Department of Medicine, University of Utah School of Medicine, Salt Lake City.

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Department of Medicine, University of Utah School of Medicine, Salt Lake City.

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Department of Medicine, University of Utah School of Medicine, Salt Lake City.

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Published January 1, 1992 - More info

Published in Volume 89, Issue 1 on January 1, 1992
J Clin Invest. 1992;89(1):197–202. https://doi.org/10.1172/JCI115563.
© 1992 The American Society for Clinical Investigation
Published January 1, 1992 - Version history
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Abstract

The central importance of xanthine dehydrogenase (XDH) and xanthine oxidase (XO) in the pathobiochemistry of a number of clinical disorders underscores the need for a comprehensive understanding of the regulation of their expression. This study was undertaken to examine the effects of cytokines on XDH/XO activity and gene expression in pulmonary endothelial cells. The results indicate that IFN-gamma is a potent inducer of XDH/XO activity in rat lung endothelial cells derived from both the microvasculature (LMVC) and the pulmonary artery. In contrast, interferon-alpha/beta, tumor necrosis factor-alpha, interleukin-1 or -6, lipopolysaccharide and phorbol myristate acetate have no demonstrable effect. The increase in XDH/XO activity requires new protein synthesis. By Northern analysis, IFN-gamma markedly increases the level of the 5.0-kb XDH/XO mRNA in LMVC. The increase is due, in part, to increased transcription rate of the XDH/XO gene. Transcriptional activation does not require new protein synthesis. The physiologic relevance of these observations was evaluated by administering IFN-gamma to rats. Intraperitoneal administration leads to an increased XDH/XO activity and XDH/XO mRNA level in rat lungs. In sum, IFN-gamma is a potent and biologically relevant inducer of XDH/XO expression; the major site of upregulation occurs at the transcriptional level.

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