The morphogenic/cytotoxic and prostaglandin-stimulating activities of interleukin-1β in the rat ovary are nitric oxide independent

I. Ben-Shlomo, E. Y. Adashi, D. W. Payne

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Nitric oxide (NO) has been implicated as a mediator of physiologic and pathologic cellular injury. Since the cytokine interleukin-1β (IL-1β) induces nitric oxide synthase (NOS) activity as well as effects morphogenic/cytotoxic changes and increased prostaglandin (PGE2) levels in cultured whole ovarian dispersates, we set out to determine whether these actions are interrelated. Treatment with IL-1β resulted in a marked increase in media nitrite and nitrate accumulation, morphological alterations, and increased release of lactate dehydrogenase (LDH) into media. Addition of IL- 1 receptor antagonist (RA) eliminated these IL-1β effects. In contrast, specific inhibitors of NOS failed to reverse IL-1β-induced morphogenic changes or LDH release in spite of complete reduction of media nitrite to control levels. Similarly, treatment with transforming growth factor β1, inhibited IL-1β-induced nitrite accumulation, but had no effect on the morphologic or cytotoxic endpoints. Moreover, the addition of sodium nitroprusside, an NO generator, resulted in progressive increments in media nitrite content without a corresponding increase in the IL-1β-associated morphogenic changes or media LDH content. Furthermore, IL-1-induced PGE2 accumulation remained unaffected by specific NOS inhibition. These observations support the view that NO does not mediate the morphogenic/cytotoxic or inflammatory-like (e.g., PGE2 inducing) properties of IL-1β in cultured whole ovarian dispersates. Although the precise role of NO in ovarian physiology remains unknown, it is possible that NO participates in the periovulatory modulation of ovarian blood flow by virtue of its potent vasodilatory activity.

Original languageEnglish
Pages (from-to)1463-1469
Number of pages7
JournalJournal of Clinical Investigation
Volume94
Issue number4
DOIs
StatePublished - Oct 1994
Externally publishedYes

Funding

FundersFunder number
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentR01HD030288

    Keywords

    • interleukin-1
    • nitric oxide
    • nitric oxide inhibitors
    • prostaglandins
    • rat ovary

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