Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and hypoxia: Role in acute lung injury

P. M. Hassoun, F. S. Yu, C. G. Cote, J. J. Zulueta, R. Sawhney, K. A. Skinner, H. B. Skinner, D. A. Parks, J. J. Lanzillo

Research output: Contribution to journalArticlepeer-review

Abstract

LPS and selected cytokines upregulate xanthine dehydrogenase/xanthine oxidase (XDH/XO) in cellular systems. However, the effect of these factors on in vivo XDH/XO expression, and their contribution to lung injury, are poorly understood. Rats were exposed to normoxia or hypoxia for 24 h after treatment with LPS (1 mg/kg) and IL-1β (100 μg/kg) or sterile saline. Lungs were then harvested for measurement of XDH/XO enzymatic activity and gene expression, and pulmonary edema was assessed by measurement of the wet/dry lung weight ratio (W/D). Although treatment with LPS + IL-1β or hypoxia independently produced a 2-fold elevation (p < 0.05 versus exposure to normoxia and treatment with saline) in lung XDH/XO activity and mRNA, the combination of LPS + IL-1β and hypoxia caused a 4- and 3.5-fold increase in these values, respectively. XDH/XO protein expression was increased 2-fold by hypoxia alone and 1.3-fold by treatment with LPS + IL-1β alone or combination treatment. Compared with normoxic lungs, W/D was significantly increased by exposure to hypoxia, LPS + IL-1β, or combination treatment. This increase was prevented by treatment of the animals with tungsten, which abrogated lung XDH/XO activity. In conclusion, LPS, IL-1β, and hypoxia significantly upregulate lung XDH/XO expression in vivo. The present data support a role for this enzyme in the pathogenesis of acute lung injury.

Original languageEnglish (US)
Pages (from-to)299-305
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume158
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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