The IL-8 production by streptococcal pyrogenic exotoxin B

Chia Wen Chang, Siang Yu Wu, Woei Jer Chuang, Yee Shin Lin, S. Y. Wu, Ching Chuan Liu, Pei Jane Tsai, Ming T. Lin

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4 Citations (Scopus)

Abstract

We have previously identified αvβ3 and Fas as receptors for the streptococcal pyrogenic exotoxin B (SPE B), and G308S, a mutant of SPE B with RSD motif, which interacts with Fas only. This study aims to evaluate how SPE B interacts with cells to induce the production of IL-8. Our results showed that following exposure to SPE B or G308S, the levels of IL-8 protein and mRNA were increased and the increase was inhibited by the addition of anti-Fas antibody, suggesting that the increased production of IL-8 by SPE B is mediated through Fas receptor. In the presence of G308S, the association of FADD and procaspase 8, and activation of NF-κB were also detected. The application of siRNA of FADD and of procaspase 8 could inhibit the NF-κB activity. The proteolytic activity of caspase 8 was required for the NF-κB activity. Further studies showed that G308S could increase the phosphorylation of ERK and the translocation of NF-κB into the nucleus, and the inhibition of ERK phosphorylation decreased the IL-8 production, mRNA expression and activation of NF-κB. In addition, siRNA of procaspase 8 could inhibit the G308S-induced cleavage of MEKK1, binding of MEKK1 to caspase 8, activation of ERK and the NF-κB activity. Taken together, the production of IL-8 by SPE B in A549 cells is mediated by Fas, and followed by the activation of FADD, caspase 8, MEKK1, ERK and NF-κB.

Original languageEnglish
Pages (from-to)1316-1326
Number of pages11
JournalExperimental Biology and Medicine
Volume234
Issue number11
DOIs
Publication statusPublished - 2009 Nov 1

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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