PPAR-α contributes to the anti-inflammatory activity of 17β-estradiol

Concetta Crisafulli, Stefano Bruscoli, Emanuela Esposito, Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Placido Bramanti, Graziella Migliorati, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review


Because studies have shown that 17β-estradiol (E2) produces anti-inflammatory effects after various adverse circulatory conditions, we have recently demonstrated that E2 significantly reduced the acute lung injury. Moreover, previous results suggest that peroxisome proliferator-activated receptor-α (PPAR-α), an intracellular transcription factor activated by fatty acids, plays a role in the control of inflammation. With the aim to characterize the role of PPAR-α in estrogen-mediated anti-inflammatory activity, we tested the efficacy of E2 in an experimental model of lung inflammation, carrageenan-induced pleurisy, comparing ovariectomized wild-type (WT) and PPAR-α lacking (PPAR-αKO) mice. Results indicate that E2-mediated anti-inflammatory activity is weakened in PPAR-αKO mice, compared with WT control groups. In particular, E2 was less effective in PPAR-αKO, compared with WT mice, in inhibition of cell migration as well as lung injury, NF-kB activation, TNF-α production, and inducible nitric-oxide synthase (iNOS) activation. Moreover, macrophages from PPAR-αKO were less susceptible to E2-induced iNOS inhibition in vitro compared with macrophages from WT mice. Moreover, the results indicate that PPAR-α was required for estrogen receptor up-regulation, following E2 treatment. These results show for the first time that PPAR-α contributes to the anti-inflammatory activity of E2.

Original languageEnglish
Pages (from-to)796-807
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
Publication statusPublished - Dec 2009

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Medicine(all)


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