Format

Send to

Choose Destination
See comment in PubMed Commons below
J Trauma Acute Care Surg. 2012 Aug;73(2):408-12. doi: 10.1097/TA.0b013e31825a789b.

17β-Estradiol attenuates cytokine-induced nitric oxide production in rat hepatocyte.

Author information

1
Department of Surgery and Price Institute of Surgical Research, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.

Abstract

OBJECTIVE:

Nitric oxide (NO) regulation during shock and sepsis is complex. NO production by endothelial NO synthase maintains microvascular perfusion and prevents shock-induced organ injury. However, the overproduction of NO by inducible NO synthase (iNOS) contributes to liver dysfunction after shock and is associated with increased tissue damage and mortality. Estrogen improves organ function and outcome after shock and sepsis, but the mechanism is unknown. We hypothesized that 17β-estradiol would improve organ function by regulating the production of hepatocyte NO.

METHODS:

Isolated rat hepatocytes were stimulated in vitro with pro-inflammatory cytokines to induce NO synthesis with or without estrogen. Nitrite was detected after 24 hours. INOS protein was determined using Western blot analysis.

RESULTS:

Cytokine stimulation increased nitrite and iNOS protein in a dose-dependent manner. The cytokine-induced nitrite increase was significantly decreased by estrogen. iNOS expression was also diminished in cultures with the higher doses of estrogen.

CONCLUSION:

17β-Estradiol decreases cytokine-stimulated iNOS expression and NO production. The down-regulation of iNOS expression may account for the beneficial role of estrogens in models of sepsis and shock.

PMID:
22846947
PMCID:
PMC3422572
DOI:
10.1097/TA.0b013e31825a789b
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Lippincott Williams & Wilkins Icon for PubMed Central
    Loading ...
    Support Center