Nitric Oxide Mediates Interleukin-1-induced Cellular Cytotoxicity in the Rat Ovary: A Potential Role for Nitric Oxide in the Ovulatory Process

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Treatment of primary cultures of rat ovarian dispersates with IL-1beta results in morphologic and cytotoxic changes, thought to reflect tissue remodeling events associated with ovulation. We examined the role that the free radical nitric oxide plays in this process and report that IL-1beta induces expression of the inducible isoform of nitric oxide synthase in ovarian cells as demonstrated by immunoprecipitation. We show that IL-1beta treatment results in the formation of nitric oxide (as measured by accumulation of nitrite and cGMP) in both a time- and concentration-dependent manner that is prevented by aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase. Aminoguanidine also inhibits IL-1-induced ovarian cellular cytotoxicity. These results suggest that nitric oxide is an important mediator of cell death and may act as a physiologically significant mediator of tissue remodeling events that occur in vivo during the ovulatory process. (J. Clin. Invest. 1993. 92:3053-3056.) Key words: cytokines. aminoguanidine. nitric oxide synthase. interleukin-1. ovulation

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