國家衛生研究院 NHRI:Item 3990099045/12682

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Title:	Truncated pneumolysin from streptococcus pneumoniae as a TLR4-Antagonizing new drug for chronic inflammatory conditions
Authors:	Chang, SF;Chen, CN;Lin, JC;Wang, HE;Mori, S;Li, JJ;Yen, CK;Hsu, CY;Fung, CP;Chong, PCS;Leng, CH;Ding, YJ;Chang, FY;Siu, LK
Contributors:	National Institute of Infectious Diseases and Vaccinology
Abstract:	Microbial proteins have recently been found to have more benefits in clinical disease treatment because of their better-developed strategy and properties than traditional medicine. In this study, we investigated the effectiveness of a truncated peptide synthesized from the C-terminal sequence of pneumolysin, i.e., C70PLY4, in Streptococcus pneumoniae, in treating chronic inflammatory conditions. It has been shown that C70PLY4 significantly blocks the transendothelial migration of neutrophils and attenuates the formation of atherosclerotic plaque and the secretion of soluble forms of the intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule 1 (VCAM-1), and E-selectin in high-fat-diet/streptozotocin-induced inflammatory rats. The mechanism and the docking simulation analysis further indicated that C70PLY4 might serve as a Toll-like receptor 4 (TLR4) antagonist by competing for the binding site of MD2, an indispensable protein for lipopolysaccharide (LPS)-TLR4 interaction signaling, on the TLR4 structure. Moreover, compared to the full-length PLY, C70PLY4 seems to have no cytotoxicity in human vascular endothelial cells. Our study elucidated a possible therapeutic efficacy of C70PLY4 in reducing chronic inflammatory conditions and clarified the underlying mechanism. Thus, our findings identify a new drug candidate that, by blocking TLR4 activity, could be an effective treatment for patients with chronic inflammatory diseases.
Date:	2020-05-09
Relation:	Cells. 2020 May 9;9(5):Article number 1183.
Link to:	http://dx.doi.org/10.3390/cells9051183
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2073-4409&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000539340200117
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85084625933
Appears in Collections:	[Leung-Kei Siu] Periodical Articles [Chih-Hsiang Leng] Periodical Articles

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