17β-estradiol antiinflammatory activity in carrageenan-induced pleurisy

S. Cuzzocrea, S. Santagati, L. Sautebin, E. Mazzon, G. Calabrò, I. Serraino, A. P. Caputi, A. Maggi

Research output: Contribution to journalArticle

Abstract

We have recently demonstrated that 17β-estradiol (E2) opposes cytokine-dependent increase of inducible nitric oxide synthase (iNOS) activity in rat smooth muscle cells and proposed that this effect might be associated to an antiinflammatory activity of this hormone. In the present study, we examine the E2 effects on a well-known in vivo model of inflammation. We show that, in carrageenan treatment of ovariectomized rats, prior exposure to E2 significantly attenuated inflammatory response as measured by histological examination and exudate production. The effect was visible with a single injection of a physiological dose of E2 1 h before the carrageenan treatment and was blocked by coadministration of the estrogen receptor antagonists ICI 182,780 or tamoxifen. This latter observation suggests that the effect is receptor mediated. The mechanisms by which estradiol has beneficial effects in this model of inflammation are unclear: we show that in hormonally treated rats there is a decrease in polymorphonuclear cells migration as shown by cell counting and myeloperoxidase measurement. In addition, E2 pretreatment opposes carrrageneen-induced high lipid peroxidation maintaining malondialdehyde activity at control levels. E2 treatment decreases NO production and the activity of iNOS with consequent diminished nitrite synthesis and nitrosine accumulation. Finally, immunohistochemical analysis for poly (ADP-ribose) synthase revealed a positive staining in lungs from carrageenantreated rats that was blocked by estradiol treatment. We conclude that E2 attenuates the degree of inflammation and tissue damage associated with carrageenan-induced pleurisy in the rat.

Original languageEnglish
Pages (from-to)1455-1463
Number of pages9
JournalEndocrinology
Volume141
Issue number4
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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    Cuzzocrea, S., Santagati, S., Sautebin, L., Mazzon, E., Calabrò, G., Serraino, I., Caputi, A. P., & Maggi, A. (2000). 17β-estradiol antiinflammatory activity in carrageenan-induced pleurisy. Endocrinology, 141(4), 1455-1463. https://doi.org/10.1210/en.141.4.1455