P. aeruginosa LPS stimulates calcium signaling and chloride secretion via CFTR in human bronchial epithelial cells

Buyck, Julien; Verrière, Valia; Benmahdi, R.; Higgins, Gerard; Guery, Benoît; Matran, Régis; Harvey, Bill; Faure, Karine; Urbach, V.

doi:10.1016/j.jcf.2012.06.007

Cited by 18 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast with these data, it has been shown that acute (15 min) application of P. aeruginosa (PA14) or purified LPS increased the rate of iodide efflux, an index of Cl − secretion, through 2WT2 epithelial cells expressing wt-CFTR [9]. Furthermore, BUYCK et al [35] have shown that P. aeruginosa LPS-stimulated Cl − currents through CFTR channels in 16HBE14o-cells, probably via a calcium signal. Similarly, N-(3-oxo-dodecanoyl)-S-homoserine lactone (3O-C12), a quorum sensing molecule secreted by P. aeruginosa, has been shown to rapidly enhance Cl − and fluid secretion as well as cytosolic calcium and cAMP levels [36].…”

Section: Discussionmentioning

confidence: 99%

Deleterious impact ofPseudomonas aeruginosaon cystic fibrosis transmembrane conductance regulator function and rescue in airway epithelial cells

et al. 2015

View full text Add to dashboard Cite

The epithelial response to bacterial airway infection, a common feature of lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis, has been extensively studied. However, its impact on cystic fibrosis transmembrane conductance regulator (CFTR) channel function is not clearly defined. Our aims were, therefore, to evaluate the effect of Pseudomonas aeruginosa on CFTR function and expression in non-cystic fibrosis airway epithelial cells, and to investigate its impact on ΔF508-CFTR rescue by the VRT-325 corrector in cystic fibrosis cells.CFTR expression/maturation was evaluated by immunoblotting and its function by short-circuit current measurements.A 24-h exposure to P. aeruginosa diffusible material (PsaDM) reduced CFTR currents as well as total and membrane protein expression of the wildtype (wt) CFTR protein in CFBE-wt cells. In CFBE-ΔF508 cells, PsaDM severely reduced CFTR maturation and current rescue induced by VRT-325. We also confirmed a deleterious impact of PsaDM on wt-CFTR currents in non-cystic fibrosis primary airway cells as well as on the rescue of ΔF508-CFTR function induced by VRT-325 in primary cystic fibrosis cells.These findings show that CFTR function could be impaired in non-cystic fibrosis patients infected by P. aeruginosa. Our data also suggest that CFTR corrector efficiency may be affected by infectious components, which should be taken into account in screening assays of correctors. @ERSpublications Exposure of airway epithelial cell to P. aeruginosa impairs CFTR function, expression and rescue by correctors http://ow.ly/IleTw

show abstract

Section: Discussionmentioning

confidence: 99%

Deleterious impact ofPseudomonas aeruginosaon cystic fibrosis transmembrane conductance regulator function and rescue in airway epithelial cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Ca 21 signals are crucial for the control of a broad range of cellular functions. 20,21 Upon TLR stimulation, intracellular calcium levels are increased, [34][35][36][37][38][39] either from internal stores in the ER lumen or from influx from the extracellular space. Previous studies have suggested that increased intracellular calcium plays important roles in mediating the TLR-triggered immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that increased intracellular calcium plays important roles in mediating the TLR-triggered immune response. [35][36][37][38][39][40][41][42][43][44][45][46][47] In most studies, attention has been paid to intracellular calcium mobilization. However, TLRs may trigger calcium release from the ER and then STIM-ORAImediated calcium entry.…”

Section: Discussionmentioning

confidence: 99%

Extracellular calcium elicits feedforward regulation of the Toll-like receptor-triggered innate immune response

et al. 2015

View full text Add to dashboard Cite

Despite the expanding knowledge on feedback regulation of Toll-like receptor (TLR) signaling, the feedforward regulation of TLR signaling for the proper innate response to invading microbes is not fully understood. Here, we report that extracellular calcium can coordinate the activation of the small GTPases Ras and Ras-proximate-1 (Rap1) upon TLR stimulation which favors activation of macrophages through a feedforward mechanism. We show that different doses of TLR agonists can trigger different levels of cytokine production, which can be potentiated by extracellular calcium but are impaired by the chelating reagent ethylene glycol tetraacetic acid (EGTA) or by knockdown of stromal interaction molecule 1 (STIM1). Upon TLR engagement, GTP-bound Ras levels are increased and GTP-bound Rap1 is decreased, which can be reversed by EGTA-mediated removal of extracellular calcium. Furthermore, we demonstrate that Rap1 knockdown rescues the inhibitory effects of EGTA on the TLR-triggered innate response. Examination of the TLR signaling pathway reveals that extracellular calcium may regulate the TLR response via feedforward activation of the extracellular signal-regulated kinase signaling pathway. Our data suggest that an influx of extracellular calcium, mediated by STIM1-operated calcium channels, may transmit the information about the intensity of extracellular TLR stimuli to initiate innate responses at an appropriate level. Our study may provide mechanistic insight into the feedforward regulation of the TLR-triggered innate immune response. Cellular & Molecular Immunology

show abstract

“…At the same time, we also found LPS can augment the Cl − current of TMEM16A by patch clamp techniques in the present study. It was also reported that LPS can augment the Cl − current of CFTR [25].…”

Section: Discussionmentioning

confidence: 90%

Increased TMEM16A Involved in Alveolar Fluid Clearance After Lipopolysaccharide Stimulation

Yan

et al. 2016

Inflammation

View full text Add to dashboard Cite

We detected the expression of TMEM16A in LA795 cells and mouse lung tissue by RT-PCR, Western blot, and RNA interference techniques. TMEM16A expression was significantly increased by LPS stimulation in LA795 cells and in mouse lung tissue. Moreover, the LPS-induced TMEM16A expression enhancement in lung tissue was much more prominent in the alveolar epithelial region than in bigger airway epithelial cells. The typical TMEM16A current was recorded, and LPS treatment significantly enhances the current amplitude in LA795 cells. TMEM16A shRNA or TMEM16A inhibitor (T16Ainh-A01) did not affect alveolar fluid clearance (AFC), while co-application of T16Ainh-A01 induced a stronger AFC inhibition than LPS alone. LPS notably and synchronously enhanced Akt phosphorylation (p-Akt) and TMEM16A expression in a time-dependent manner in LA795 cells. Taken together, our results suggest that TMEM16A maybe plays an important role in pathological conditions of LPS-induced ALI as a protective protein.

show abstract

P. aeruginosa LPS stimulates calcium signaling and chloride secretion via CFTR in human bronchial epithelial cells

Cited by 18 publications

References 29 publications

Deleterious impact ofPseudomonas aeruginosaon cystic fibrosis transmembrane conductance regulator function and rescue in airway epithelial cells

Deleterious impact ofPseudomonas aeruginosaon cystic fibrosis transmembrane conductance regulator function and rescue in airway epithelial cells

Extracellular calcium elicits feedforward regulation of the Toll-like receptor-triggered innate immune response

Increased TMEM16A Involved in Alveolar Fluid Clearance After Lipopolysaccharide Stimulation

Contact Info

Product

Resources

About