Mechanism of the salutary effects of 17β-estradiol following trauma-hemorrhage: Direct downregulation of Kupffer cell proinflammatory cytokine production

Yukihiro Yokoyama, Joachim F. Kuebler, Takeshi Matsutani, Martin G. Schwacha, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Kupffer cells have been reported as a major source of proinflammatory cytokines (i.e. IL-6, TNF-α), which have been implicated in the pathogenesis of trauma-hemorrhage. Previous studies have shown a protective effect of 17β-estradiol on immune function and physiological responses following trauma-hemorrhage. In this study, we investigated whether 17β-estradiol has a direct effect on Kupffer cell cytokine production following trauma-hemorrhage. Male Sprague-Dawley rats were subjected to trauma (midline laparotomy) and hemorrhage (35-40 mmHg for 90 min followed by fluid resuscitation) or sham operation. Two hours later, Kupffer cells were isolated and cultured with 17β-estradiol in the presence and absence of lipopolysaccharide stimulation. Kupffer cell IL-6 and TNF-α production increased following trauma-hemorrhage. Incubation with 17β-estradiol attenuated the production of IL-6 by cells from both sham and trauma-hemorrhage animals in a dose-dependent manner. The suppression of IL-6 production by 17β-estradiol was paralleled by a decrease in mRNA levels. In contrast to IL-6, the effects of 17β-estradiol on TNF-α production were minimal. In conclusion, these results indicate the direct downregulation of Kupffer cell IL-6 production by 17β-estradiol at a molecular level, which might explain in part the previously observed salutary effects of estradiol treatment following trauma-hemorrhage.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalCytokine
Volume21
Issue number2
DOIs
StatePublished - Jan 21 2003
Externally publishedYes

Keywords

  • Hemorrhage
  • IL-6
  • Kupffer cell
  • Proinflammatory cytokine
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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