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

10 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)914-922
頁數9
期刊Toxicon
50
發行號7
DOIs
出版狀態已發佈 - 十二月 1 2007

指紋

Macrophages
Phospholipases A2
Venoms
Lipopolysaccharides
Crotalid Venoms
Chemokine CCL5
Phosphorylation
Phospholipases
Transcription
Titration
Sepsis
Anti-Inflammatory Agents
Chemical activation
Membranes
Degradation
Polymerase Chain Reaction
Proteins

ASJC Scopus subject areas

  • Toxicology

引用此文

Binding of a venom Lys-49 phospholipase A2 to LPS and suppression of its effects on mouse macrophages. / Tsai, Shu-Huei; Chen, Yen-Chou; Chen, Linda; Wang, Ying Ming; Tsai, Inn Ho.

於: Toxicon, 卷 50, 編號 7, 01.12.2007, p. 914-922.

研究成果: 雜誌貢獻文章

Tsai, Shu-Huei ; Chen, Yen-Chou ; Chen, Linda ; Wang, Ying Ming ; Tsai, Inn Ho. / Binding of a venom Lys-49 phospholipase A2 to LPS and suppression of its effects on mouse macrophages. 於: Toxicon. 2007 ; 卷 50, 編號 7. 頁 914-922.
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abstract = "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.",
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AU - Tsai, Inn Ho

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