https://scholars.lib.ntu.edu.tw/handle/123456789/564112
標題: | Snake Venom Disintegrin Inhibits the Activation of Toll-Like Receptors and Alleviates Sepsis through Integrin alphaVbeta3 Blockade | 作者: | Hsu C.-C. Chuang W.-J. Chung C.-H. Chang C.-H. Peng H.-C. TUR-FU HUANG |
公開日期: | 2016 | 卷: | 6 | 起(迄)頁: | 23387 | 來源出版物: | Scientific Reports | 摘要: | Bacterial infection-induced sepsis is the leading cause of septic inflammatory disease. Rhodostomin (Rn), a snake venom disintegrin, was previously reported to interact with the αVβ3 integrin and the TLR4 on phagocyte in attenuating LPS-induced endotoxemia. In this report, we further evaluated the effects of Rn on TLR2-activated monocytes and its in vivo efficacy. Rn effectively suppressed the adhesion, migration, and cytokine release of Pam3CSK4-activated THP-1 cells. Rn specifically bound to integrin αVβ3 of TLR2-activated THP-1. Integrin αV and Akt siRNA transfection both restrained Pam3CSK4-elicited cytokine release. Rn decreased the Pam3CSK4-induced phosporylation of MAPKs, degradation of I?° B and activation of FAK, Akt, c-Src and Syk. The Pam3CSK4-induced translocation of MyD88, a central adaptor of TLR2, to the cell membrane was also inhibited by Rn treatment. In the polymicrobial inflammatory caecal ligation and puncture model, Rn significantly reduced pro-inflammatory cytokine and chemokine release, alleviated tissue injury and elevated survival rate in vivo. Taken together, in addition to inhibiting the activation of TLR4, Rn exhibits anti-inflammatory activity through antagonizing the activation of phagocytes and interrupting the crosstalk between αVβ3 and TLR2-dependent signaling pathways. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/564112 | ISSN: | 20452322 | DOI: | 10.1038/srep23387 | SDG/關鍵字: | chemokine; cytokine; peptide; rhodostomin; Tlr2 protein, mouse; toll like receptor 2; vitronectin receptor; animal; cell adhesion; cell line; cell motion; cytology; disease model; drug effects; gene expression regulation; human; male; metabolism; monocyte; mouse; sepsis; signal transduction; Animals; Cell Adhesion; Cell Line; Cell Movement; Chemokines; Cytokines; Disease Models, Animal; Gene Expression Regulation; Humans; Integrin alphaVbeta3; Male; Mice; Monocytes; Peptides; Sepsis; Signal Transduction; Toll-Like Receptor 2 |
顯示於: | 藥理學科所 |
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