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Thromb Haemost 2005; 93(05): 940-948
DOI: 10.1160/TH04-03-0195
Wound Healing and Inflammation/Infection
Schattauer GmbH

A potential role of YC-1 on the inhibition of cytokine release in peripheral blood mononuclear leukocytes and endotoxemic mouse models

Shiow-Lin Pan
1   Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Jih-Hwa Guh
2   School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Chieh-Yu Peng
1   Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Ya-Ling Chang
1   Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Fong-Chi Cheng
3   MDS Pharma Service, Taipei, Taiwan
,
Jau-Hsiang Chang
4   Yung-Shin Pharmaceutical Industry Co, Ltd, Taichung, Taiwan
,
Sheng-Chu Kuo
5   Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan
,
Fang-Yu Lee
4   Yung-Shin Pharmaceutical Industry Co, Ltd, Taichung, Taiwan
,
Che-Ming Teng
1   Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
› Author AffiliationsShiow-Lin Pan and Jih-Hwa Guh contributed equally to this work
Further Information

Publication History

Received 30 March 2004

Accepted after resubmission 26 January 2005

Publication Date:
11 December 2017 (online)

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Summary

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.

Keywords

YC-1 - lipopolysaccharide - nuclear factor-κB
 

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