P. aeruginosa drives CXCL8 synthesis via redundant toll-like receptors and NADPH oxidase in CFTR∆F508 airway epithelial cells

Abstract

These results demonstrate that NADPH oxidase is necessary for CXCL8 synthesis in response to TLRs activation by P. aeruginosa.

The Protein Kinase TPL2 Is Essential for ERK1/ERK2 Activation and Cytokine Gene Expression in Airway Epithelial Cells Exposed to Pathogen-Associated Molecular Patterns (PAMPs)

“…PsaDM activate p38α in a TLR-dependent fashion, acting mainly through TLR5 and TLR2 [15], [21], [22]. Therefore we checked whether activation of ERK1/ERK2 in BEAS-2B AECs occurs via the same mechanism when they are stimulated with isolated TLR ligands.…”

Proinflammatory cytokine secretion is suppressed by TMEM16A or CFTR channel activity in human cystic fibrosis bronchial epithelia

“…The question of whether hyperinflammation is a sole consequence of ASL dehydration and bacterial colonization or whether these processes can be primed by the CFTR functional expression defect has been extensively investigated by a number of laboratories but remains controversial (Pizurki et al ., 2000; Ribeiro et al ., 2005; Hybiske et al ., 2007; Fulcher et al ., 2009; Vandivier et al ., 2009; Roussel et al ., 2011). Several factors could account for the conflicting results.…”

“…It is intriguing that pancreas in newborn CF pigs shows hallmarks of increased immune and inflammatory response without apparent infection (Abu-El-Haija et al ., 2011). Elevated interleukin-8 (IL-8) production has been reported in CF cell lines and primary cultures both constitutively and after activation of Toll-like or tumor necrosis factor α receptors, implying a CFTR-dependent alteration in the innate immune response (Ribeiro et al ., 2005; Vandivier et al ., 2009; Roussel et al ., 2011). However, this could not be reproduced in some cellular models (Pizurki et al ., 2000; Hybiske et al ., 2007; Fulcher et al ., 2009), whereas in others the CFTR appeared to have a permissive role in IL-8 secretion (John et al ., 2010, 2011).…”

Atypical Activation of the Unfolded Protein Response in Cystic Fibrosis Airway Cells Contributes to p38 MAPK-Mediated Innate Immune Responses

“…Three general mechanisms have evolved to restore ER homeostasis-increase in the protein folding capacity, attenuation of translation, and upregulation of the degradation machinery (ER-associated degradation, autophagy) (43). It is important to appreciate that in addition to misfolding of mutated CFTR protein, many factors are likely to have an impact on proteostasis to trigger ER stress in CF, including oxidative stress (11,16,17,(44)(45)(46), chronic infection (47), and decreased functionality of ER stress relief mechanisms, such as autophagy (21). Nevertheless, the literature contains conflicting results concerning the presence of ER stress in CF and the potential contribution of ER stress to CF inflammatory disease.…”