Snake Venom Disintegrin Inhibits the Activation of Toll-Like Receptors and Alleviates Sepsis through Integrin alphaVbeta3 Blockade

Chun Chieh Hsu, Woei Jer Chuang, Ching Hu Chung, Chien Hsin Chang, Hui Chin Peng, Tur Fu Huang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 Iΰ 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.

Original languageEnglish
Article number23387
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Mar 18

Fingerprint

Integrin alphaVbeta3
Disintegrins
Snake Venoms
Toll-Like Receptors
Sepsis
Integrins
Phagocytes
Cytokines
Endotoxemia
rhodostomin
Punctures
Chemokines
Bacterial Infections
Small Interfering RNA
Transfection
Ligation
Monocytes
Anti-Inflammatory Agents
Cell Membrane

All Science Journal Classification (ASJC) codes

  • General

Cite this

Hsu, Chun Chieh ; Chuang, Woei Jer ; Chung, Ching Hu ; Chang, Chien Hsin ; Peng, Hui Chin ; Huang, Tur Fu. / Snake Venom Disintegrin Inhibits the Activation of Toll-Like Receptors and Alleviates Sepsis through Integrin alphaVbeta3 Blockade. In: Scientific reports. 2016 ; Vol. 6.
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Snake Venom Disintegrin Inhibits the Activation of Toll-Like Receptors and Alleviates Sepsis through Integrin alphaVbeta3 Blockade. / Hsu, Chun Chieh; Chuang, Woei Jer; Chung, Ching Hu; Chang, Chien Hsin; Peng, Hui Chin; Huang, Tur Fu.

In: Scientific reports, Vol. 6, 23387, 18.03.2016.

Research output: Contribution to journalArticle

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AU - Huang, Tur Fu

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