Binding of a venom Lys-49 phospholipase A2 to LPS and suppression of its effects on mouse macrophages

Shu-Huei Tsai, Yen-Chou Chen, Linda Chen, Ying Ming Wang, Inn Ho Tsai

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)


The Lys49-phospholipases A2 (K49-PLAs) are abundant in many pit vipers' venom. They are highly basic myotoxins and capable of binding membranes but lack hydrolytic activity. Considerable attention has been directed to its antibacterial activity but the exact mechanisms remain unclear. We now evaluate the roles of a K49-PLA from Trimeresurus stejnegeri venom in antagonizing the effects of lipopolysaccharide (LPS) on mouse macrophages (RAW264.7 cells). The K49-PLA markedly reduced LPS-stimulated production of NO, MCP-1, RANTES, and iNOS. RT-PCR analysis also confirmed its suppression of LPS-induced transcription of these cellular proteins. Moreover, LPS-induced activation of NFκB was dramatically abolished, while phosphorylation and degradation of IκB were also inhibited. Other types of venom phospholipases tested did not show the same effects as K49-PLA. Finally, strong binding between K49-PLA and LPS with a dissociation constant at the order of 10 nM was shown by microcalorimetry titration. These findings provide unprecedented evidence that a low dose of K49-PLA possesses potent anti-inflammatory and antibacterial properties, which raises the prospect of a new therapeutic approach against sepsis.
頁(從 - 到)914-922
出版狀態已發佈 - 12月 1 2007

ASJC Scopus subject areas

  • 毒理學


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