Streptococcal pyrogenic exotoxin B-induced apoptosis in A549 cells is mediated through αvβ3 integrin and Fas

Wan Hua Tsai, Chia Wen Chang, Yee Shin Lin, Woei Jer Chuang, Jiunn Jong Wu, Ching Chuan Liu, Pei Jane Tsai, Ming T. Lin

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14 Citations (Scopus)

Abstract

Our previous work suggested that streptococcal pyrogenic exotoxin (SPE) B-induced apoptosis is mediated through a receptor-like mechanism. In this study, we have identified αvβ3 and Fas as the SPE B receptors for this function. The SPE B fragment without the RGD motif and G308S, a SPE B mutant with the RSD motif, induced less apoptosis than did native SPE B, suggesting that the RGD motif is critical for SPE B-induced apoptosis. Fluorescein isothiocyanate-SPE B binding assays and immunoprecipitation analysis showed that SPE B specifically interacted with αvβ 3. Anti-αvβ3 antibody partially inhibited SPE B-induced apoptosis but had no effect on G308S-induced apoptosis. In addition, Fas binding to SPE B was verified in an affinity column and an immunoprecipitation analysis. Anti-Fas antibody inhibited SPE B- and G308S-induced apoptosis in a dose-dependent manner, suggesting that Fas-mediated SPE B-induced apoptosis also occurs RGD independently. Both anti-αvβ3 and anti-Fas antibodies synergistically inhibited SPE B-induced apoptosis. The apoptotic cascades were activated by SPE B and G308S, with a little delay by the latter. After SPE B binding, the cell surface level of αvβ3, but not of Fas, was decreased. The decreased αvβ3 level was restored by treatment with the proteasome inhibitor MG132, suggesting a SPE B-mediated endocytosis of integrin αvβ3 via the ubiquitin-proteasome system. Taken together, our results demonstrate that SPE B-induced apoptosis is mediated through αvβ 3 integrin and Fas in a synergistic manner.

Original languageEnglish
Pages (from-to)1349-1357
Number of pages9
JournalInfection and Immunity
Volume76
Issue number4
DOIs
Publication statusPublished - 2008 Apr

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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