Chlamydia inhibit host cell apoptosis by inducing Bag-1 via the MAPK/ERK survival pathway

Abstract

Chlamydia are obligate intracellular bacteria that frequently cause human disease. Host cells infected with Chlamydia are profoundly resistant to diverse apoptotic stimuli. The inhibition of apoptosis is thought to be an important immune escape mechanism allowing Chlamydia to productively complete their obligate intracellular growth cycle. Chlamydial antiapoptotic activity involves activation of the MAPK/ERK survival pathway. However, the molecular mechanisms are not well understood. Here we show that Bag-1 is up-regulated in Chlamydia-infected cells. U0126 and GW5074 suppress the induction of Bag-1 by Chlamydia, implying that Chlamydia may up-regulate Bag-1 via the MAPK/ERK survival pathway. Overexpression of Bag-1 is sufficient to protect against apoptosis, while depletion of Bag-1 suppresses the antiapoptotic effect of Chlamydia. The data indicate Chlamydia may up-regulate Bag-1 through the MAPK/ERK survival pathway to suppress apoptosis.

Mechanisms of apoptosis inhibition in Chlamydia pneumoniae-infected neutrophils

“…Activation of ERK1/2 also modulates apoptosis by preventing activation of caspase-8 (Pluskota et al, 2008;Zhang et al, 2003). C. trachomatis can modulate host cell apoptosis by upregulating the Bcl-2-associated athanogene (Bag-1) expression via the MAPK/ERK pathway (Kun et al, 2013). Therefore, activation of ERK1/2 in C. pneumoniae-infected neutrophils is likely mediated by the effect on BAD, caspase-8 and/or Bag-1.…”

“…Secreted IL-8 contributes to apoptosis delay possibly in an autocrine manner. gets activated in Chlamydia-infected cells and it is well known that ERK1/2 pathway functions as an important regulator for NF-B activation and downstream cytokine release in neutrophils (Cloutier et al, 2007;Cowburn et al, 2004;Kun et al, 2013;Rajalingam et al, 2008). Therefore, the NF-B-dependent release of IL-8 is one of the downstream events in the activation of the PI3K/Akt and ERK1/2 survival pathways in C. pneumoniae-infected neutrophils.…”

Cord Blood Mesenchymal Stromal Cell-Conditioned Medium Protects Endothelial Cells via STAT3 Signaling

“…In our model, STAT3 was prominently activated in HUVECs in the presence of CBMSC-conditioned medium, and when STAT3 phosphorylation was blocked, the beneficial effect was completely abolished. Induction of anti-apoptotic genes BCL-2, BCL-XL or BAG-1 is one mechanism by which these pathways can promote survival of injured cells [30,31,32]. While BCL-XL and BAG-1 were up-regulated in HUVECs as endogenous response to glucose/serum deprivation, BCL-2 expression was triggered by CBMSC-released factors in the medium.…”

Chlamydia cell biology and pathogenesis

“…Chlamydia spp. can block intrinsic apoptosis through numerous mechanisms including the MDM2-mediated ubiquitylation and proteasomal degradation of the tumour suppressor p53 (REFS 105,106), the sequestration of pro-apoptotic protein kinase Cδ (PKCδ) or BCL-2-associated agonist of cell death (BAD) to the inclusion membrane through diacylglcerol or 14-3-3β-binding Incs, respectively 49,81 , and the upregulation or stabilization of anti-apoptotic proteins including BAG family molecular chaperone regulator 1 (BAG1), myeloid leukaemia cell differentiation protein 1 (MCL1) or cIAP2 (also known as BIRC3) 7,107 . C. trachomatis inhibits extrinsic apoptosis by blocking the activation of caspase 8 through the master regulator cellular FLICE-like inhibitory protein (cFLIP; also known as caspase 8-inhibitory protein) 108 .…”