A potential role of YC-I on the inhibition of cytokine release in peripheral blood mononuclear leukocytes and endotoxemic mouse models

Shiow Lin Pan, Jin Hwa Guh, Chieh Yu Peng, Ya Ling Chang, Fong Chi Cheng, Jau Hsiang Chang, Sheng Chu Kuo, Fang Yu Lee, Che Ming Teng

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

To evaluate the anti-sepsis potential of YC-1, we have examined the effect of YC-1 on the regulation of cytokine production in human leukocytes and endotoxemic mice. The data demonstrated that YC-1 showed a preferential inhibition on proinflammatory cytokine production without inhibition of cell growth or induction of cytotoxicity in human leukocytes. On the other hand, in the septic mouse model, treatment with an intraperitoneal application of LPS caused a cumulative death within 27 hours. The post-treatment administration of YC-1 significantly increased the survival rate in endotoxemic mice. Furthermore, several mediators were detected and the data showed that YC-1 profoundly blocked LPS-induced NO as well as TNF-α production, and prevented lung damage by histological examination. Samples from the animal model showed that LPS-induced NF-κB/DNA binding activity and consequent up-regulation of iNOS expression in tissues were abolished by post-administration of YC-1. Furthermore, YC-1, by itself, did not modify cGMP content while significantly inhibit LPS-induced cGMP formation, suggesting that YC-1-mediated effect was not through a cGMP-elevating pathway.Taken together, it is evident that the post-treatment administration of YC-1 after LPS application significantly inhibits NF-κB activation, iNOS expression, NO over-production, and cytokine release reaction resulting in an improved survival rate in endotoxemic mice. It is suggested that YC-1 may be a potential agent for the therapeutic treatment of sepsis.

Original languageEnglish
Pages (from-to)940-948
Number of pages9
JournalThrombosis and Haemostasis
Volume93
Issue number5
DOIs
Publication statusPublished - May 2005
Externally publishedYes

Keywords

  • Lipopolysaccharide
  • Nuclear factor-κB
  • YC-I

ASJC Scopus subject areas

  • Hematology

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