XANTHINE OXIDOREDUCTASE IN HUMAN MAMMARY EPITHELIAL-CELLS - ACTIVATION IN RESPONSE TO INFLAMMATORY CYTOKINES

Xanthine oxidoreductase (XOR) in human mammary epithelial cells was sh own to have low true specific activity, similar to that in breast milk . Enzymic activity was increased in response to inflammatory cytokines ; increases of 2-2.5-fold being seen with TNF-alpha and IL-1 beta and of approximately 8-fold with IFN-gamma. No significant increase was se en with IL-6. A combination of IFN-gamma and TNF-alpha, or of these tw o cytokines plus IL-1 beta, led to responses representing the sum of t hose obtained by using the individual cytokines. The 8-fold increase i n enzymic activity, stimulated by IFN-gamma, corresponded to only a 2- 3-fold increase in specific mRNA, suggesting the possibility of post-t ranslational activation; a possibility strongly supported by the corre sponding 2-3-fold rise in XOR protein, as determined by ELISA. In no c ase was cytokine-induced activation accompanied by changes in the oxid ase-dehydrogenase ratio of XOR. These data strongly support a role for XOR in the inflammatory response of the human mammary epithelial cell , and provide further evidence of post-translational activation of a l ow activity form of human XOR, similar to that previously observed in vivo for the breast milk enzyme. (C) 1998 Elsevier Science B.V. All ri ghts reserved.