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Rhodostomin (Rn), a snake venom disintegrin, was previously reported to interact with the \u03b1V\u03b23 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 <jats:italic>in vivo<\/jats:italic> efficacy. Rn effectively suppressed the adhesion, migration and cytokine release of Pam3CSK4-activated THP-1 cells. Rn specifically bound to integrin \u03b1V\u03b23 of TLR2-activated THP-1. Integrin \u03b1V and Akt siRNA transfection both restrained Pam3CSK4-elicited cytokine release. Rn decreased the Pam3CSK4-induced phosporylation of MAPKs, degradation of I\u03baB 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 <jats:italic>in vivo<\/jats:italic>. 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 \u03b1V\u03b23 and TLR2-dependent signaling pathways.<\/jats:p>","DOI":"10.1038\/srep23387","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T10:07:43Z","timestamp":1458295663000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Snake Venom Disintegrin Inhibits the Activation of Toll-Like Receptors and Alleviates Sepsis through Integrin alphaVbeta3 Blockade"],"prefix":"10.1038","volume":"6","author":[{"given":"Chun-Chieh","family":"Hsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woei-Jer","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Hu","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hsin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Chin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tur-Fu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,18]]},"reference":[{"key":"BFsrep23387_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","volume":"20","author":"CA Janeway Jr.","year":"2002","unstructured":"Janeway, C. 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