Streptococcal Pyrogenic Exotoxin B-Induced Apoptosis in A549 Cells Is Mediated through α v β 3 Integrin and Fas
| Autor: | Wan Hua Tsai, Jiunn Jong Wu, Woei Jer Chuang, Pei Jane Tsai, Ming T. Lin, Yee Shin Lin, Ching Chuan Liu, Chia Wen Chang |
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| Rok vydání: | 2008 |
| Předmět: |
Programmed cell death
Immunoprecipitation Immunology Down-Regulation Exotoxins Apoptosis Biology medicine.disease_cause Microbiology chemistry.chemical_compound Bacterial Proteins Cell Line Tumor MG132 medicine Humans fas Receptor Receptor RGD motif Integrin alphaVbeta3 Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Molecular biology Infectious Diseases chemistry Parasitology Exotoxin Protein Binding |
| Zdroj: | Infection and Immunity. 76:1349-1357 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01162-07 |
| Popis: | 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 α v β 3 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 α v β 3 . Anti-α v β 3 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-α v β 3 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 α v β 3 , but not of Fas, was decreased. The decreased α v β 3 level was restored by treatment with the proteasome inhibitor MG132, suggesting a SPE B-mediated endocytosis of integrin α v β 3 via the ubiquitin-proteasome system. Taken together, our results demonstrate that SPE B-induced apoptosis is mediated through α v β 3 integrin and Fas in a synergistic manner. |
| Databáze: | OpenAIRE |
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