Streptococcal pyrogenic exotoxin B-induced apoptosis in A549 cells is mediated by a receptor- and mitochondrion-dependent pathway

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

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9 Citations (Scopus)

Abstract

It has been shown that streptococcal pyrogenic exotoxin B (SPE B) can induce cells to undergo apoptosis. The present study is to dissect the role of SPE B protease and SPE B protein in the apoptotic process of A549 cells and to elucidate the SPE B-induced apoptotic pathway. Recombinant SPE B (rSPE B) and C192S, a mutant of SPE B without protease activity, were expressed in Escherichia coli and purified by using an affinity column. The apoptosis of A549 cells was assayed by propidium iodide staining, followed by flow cytometry analysis. Our results showed that SPE B induced apoptosis in a dose-dependent manner, whereas C192S did not. When cells were pretreated with rSPE B (2 μg/ml) for as briefly as 5 min and then incubated with C192S of 28 kDa, an apoptosis that is proportional to the period of pretreatment was observed but not with C192S of 42 kDa. These results suggest that the extracellular protease activity of rSPE B is required for the initiation of apoptosis and that the size of SPE B is important for an effective induction of apoptosis. The time course analysis revealed that molecules activated in apoptosis were in the following order: caspase-8 (1.5 h), t-Bid (2.5 h), Bax (3 h), cytochrome c release (6 h), caspase-9 (7 h), and caspase-3 (8 h). The overexpression of Bcl-2 inhibited depolarization of mitochondrial membrane, cytochrome c release, and apoptosis. The results of the present study suggest that SPE B-induced apoptosis is mediated through a receptor-like mechanism and a mitochondrion-dependent pathway.

Original languageEnglish
Pages (from-to)7055-7062
Number of pages8
JournalInfection and Immunity
Volume72
Issue number12
DOIs
Publication statusPublished - 2004 Dec

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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