Soluble epoxide hydrolase: Regulation by estrogen and role in the inflammatory response to cerebral ischemia

Ines Koerner, Wenri Zhang, Jian Cheng, Susan Parker, Patricia D. Hurn, Nabil Alkayed

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The protection from ischemic brain injury enjoyed by females is linked to the female sex hormone 17beta-estradiol. We tested the hypothesis that neuroprotection by estradiol entails the prevention of ischemia-induced inflammatory response, through suppression of the P450 eicosanoids-metabolizing enzyme soluble epoxide hydrolase (sEH). Ovariectomized female rats with and without estradiol replacement underwent 2-hour middle cerebral artery occlusion (MCAO). SEH expression was determined using Western blot, and inflammatory cytokine mRNA levels were measured at 6, 24 and 48 hours after MCAO. Cytokine mRNA was also measured in sEH-knockout mice, and in rats treated with sEH inhibitors. Estradiol reduced basal and post-ischemic sEH expression. MCAO strongly induced mRNA levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 1beta, which was attenuated in sEH-knockouts, but not by sEH inhibitors. Estradiol replacement exhibited a bimodal effect on cytokine mRNA, with increased early and reduced delayed expression. While estradiol suppresses cerebral sEH expression, and sEH suppression diminishes inflammation after MCAO, our findings suggest that the effect of estrogen on inflammation is complex, and only partially explained by sEH suppression.

Original languageEnglish (US)
Pages (from-to)2833-2841
Number of pages9
JournalFrontiers in bioscience : a journal and virtual library
Volume13
Issue number8
DOIs
StatePublished - 2008

Fingerprint

Epoxide Hydrolases
Brain Ischemia
Estrogens
Estradiol
Middle Cerebral Artery Infarction
Messenger RNA
Cytokines
Rats
Inflammation
Eicosanoids
Gonadal Steroid Hormones
Interleukin-1beta
Knockout Mice
Brain Injuries
Interleukin-6
Brain
Ischemia
Tumor Necrosis Factor-alpha
Western Blotting

Keywords

  • Cerebral ischemia
  • EETs
  • Eicosanoids
  • Epoxygenase
  • Estrogen
  • Inflammatory cytokines
  • Interleukins
  • Neuroprotection
  • Soluble epoxide hydrolase
  • TNF-alpha

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Medicine(all)

Cite this

Soluble epoxide hydrolase : Regulation by estrogen and role in the inflammatory response to cerebral ischemia. / Koerner, Ines; Zhang, Wenri; Cheng, Jian; Parker, Susan; Hurn, Patricia D.; Alkayed, Nabil.

In: Frontiers in bioscience : a journal and virtual library, Vol. 13, No. 8, 2008, p. 2833-2841.

Research output: Contribution to journalArticle

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