c-Jun NH2-terminal kinase-mediated signaling is essential for Pseudomonas aeruginosa ExoS-induced apoptosis.

Infection and Immunity
Jinghua JiaShouguang Jin

Abstract

As an opportunistic bacterial pathogen, Pseudomonas aeruginosa mainly affects immunocompromised individuals as well as patients with cystic fibrosis. In a previous study, we showed that ExoS of P. aeruginosa, when injected into host cells through a type III secretion apparatus, functions as an effector molecule to trigger apoptosis in various tissue culture cells. Here, we show that injection of the ExoS into HeLa cells activates c-Jun NH(2)-terminal kinase (JNK) phosphorylation while shutting down ERK1/2 and p38 phosphorylation. Inhibiting JNK activation by expression of a dominant negative JNK1 or with a specific JNK inhibitor abolishes ExoS-triggered apoptosis, demonstrating the requirement for JNK-mediated signaling. Following JNK phosphorylation, cytochrome c is released into the cytosol, leading to the activation of caspase 9 and eventually caspase 3. Although c-Jun phosphorylation is also observed as a result of JNK activation, ongoing host protein synthesis is not essential for the apoptotic induction, suggesting that c-Jun- or other AP-1-driven activation of gene expression is dispensable in this process. Therefore, ExoS has opposing effects on different cellular pathways that regulate apoptosis: it shuts down host cel...Continue Reading

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Citations

Dec 28, 2006·Apoptosis : an International Journal on Programmed Cell Death·J H WangB Y Chen
Sep 13, 2006·Infection and Immunity·Jinghua JiaShouguang Jin
Nov 16, 2010·Journal of Bacteriology·Yongxin JinShouguang Jin
May 10, 2008·American Journal of Respiratory and Critical Care Medicine·Ali A El SolhKristie Szarpa
Jan 28, 2014·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Jun OkudaNaomasa Gotoh
Apr 29, 2015·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Josef GoldufskySasha H Shafikhani
Jan 27, 2009·Current Opinion in Microbiology·Joanne Engel, Priya Balachandran
Jul 27, 2006·Journal of Lipid Research·Florita C HendersonRama K Mallampalli
Feb 9, 2012·Molecular BioSystems·Mariateresa VitielloMassimiliano Galdiero
Nov 8, 2005·Microbiology·Jaewha KimShouguang Jin
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seobo SimMyeong Heon Shin

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