Arylhydrocarbon receptor (AhR) activation in airway epithelial cells induces MUC5AC via reactive oxygen species (ROS) production

2011 ◽  
Vol 24 (1) ◽  
pp. 133-140 ◽  
Author(s):  
Takahito Chiba ◽  
Hiroshi Uchi ◽  
Gaku Tsuji ◽  
Hisaki Gondo ◽  
Yoichi Moroi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Reactive Oxygen ◽  
Airway Epithelial Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Airway Epithelial ◽  
Arylhydrocarbon Receptor

scholarly journals Lipid-soluble components in cigarette smoke induce mitochondrial production of reactive oxygen species in lung epithelial cells

2009 ◽  
Vol 297 (1) ◽  
pp. L109-L114 ◽  
Author(s):  
Marco van der Toorn ◽  
Delaram Rezayat ◽  
Henk F. Kauffman ◽  
Stephan J. L. Bakker ◽  
Rijk O. B. Gans ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Gaseous Phase ◽  
Mitochondrial Function ◽  
A549 Cells ◽  
Reactive Oxygen ◽  
Airway Epithelial Cells ◽  
Oxygen Species ◽  
Airway Epithelial

Reactive oxygen species (ROS) present in cigarette smoke (CS) are thought to contribute to the development of COPD. Although CS-ROS can hardly enter airway epithelial cells, and certainly not the circulation, systemic levels of ROS have been found to be elevated in COPD patients. We hypothesize that lipophilic components present in CS can enter airway epithelial cells and increase intracellular ROS production by disturbing mitochondrial function. Different airway epithelial cells were exposed to CS extract (CSE), hexane-treated CSE (CSE without lipophilic components), gaseous-phase CS, and water-filtered CS (gaseous-phase CS without ROS). Mitochondrial membrane potential (Δψm) and ATP levels were assessed using the bronchial epithelial cell line Beas-2b. ROS generation measured directly by DCF fluorescence and indirectly by measuring free thiol groups (-SH) upon exposure to CS was assessed using lung alveolar epithelial cells devoid of functional mitochondria (A549-ρ0), with normal A549 cells serving as controls. In Beas-2b cells, CSE (4 h) caused a dose-dependent decrease in Δψm and ATP levels, whereas hexane-treated CSE did not. DCF fluorescence in A549 cells increased in response to CSE, whereas this was not the case in A549-ρ0 cells. Exposure of A549 cells to CS resulted in a rapid decrease in free -SH, whereas exposure to ROS-depleted CS only resulted in a delayed decrease. This delayed decrease was less pronounced in A549-ρ0 cells. Lipophilic components in CS disturb mitochondrial function, which contributes to increased intracellular generation of ROS. Our results are of importance in understanding the systemic effects of smoking observed in patients with COPD.

scholarly journals Nlrx1-Regulated Defense and Metabolic Responses to Aspergillus fumigatus Are Morphotype and Cell Type Specific

2021 ◽  
Vol 12 ◽  
Author(s):  
Bridget Kastelberg ◽  
Tariq Ayubi ◽  
Nuria Tubau-Juni ◽  
Andrew Leber ◽  
Raquel Hontecillas ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Epithelial Cells ◽  
Aspergillus Fumigatus ◽  
Airway Epithelial Cells ◽  
Oxygen Species ◽  
Airway Epithelial ◽  
Cell Type ◽  
Immune Signaling ◽  
Cell Type Specific

The Nlr family member X1 (Nlrx1) is an immuno-metabolic hub involved in mediating effective responses to virus, bacteria, fungi, cancer, and auto-immune diseases. We have previously shown that Nlrx1 is a critical regulator of immune signaling and mortality in several models of pulmonary fungal infection using the clinically relevant fungus Aspergillus fumigatus. In the absence of Nlrx1, hosts produce an enhanced Th2 response primarily by CD103+ dendritic cell populations resulting in enhanced mortality via immunopathogenesis as well as enhanced fungal burden. Here, we present our subsequent efforts showcasing loss of Nlrx1 resulting in a decreased ability of host cells to process A. fumigatus conidia in a cell-type-specific manner by BEAS-2B airway epithelial cells, alveolar macrophages, bone marrow-derived macrophages, but not bone marrow-derived neutrophils. Furthermore, loss of Nlrx1 results in a diminished ability to generate superoxide and/or generic reactive oxygen species during specific responses to fungal PAMPs, conidia, and hyphae. Analysis of glycolysis and mitochondrial function suggests that Nlrx1 is needed to appropriately shut down glycolysis in response to A. fumigatus conidia and increase glycolysis in response to hyphae in BEAS-2B cells. Blocking glycolysis and pentose phosphate pathway (PPP) via 2-DG and NADPH production through glucose-6-phosphate dehydrogenase inhibitor resulted in significantly diminished conidial processing in wild-type BEAS-2B cells to the levels of Nlrx1-deficient BEAS-2B cells. Our findings suggest a need for airway epithelial cells to generate NADPH for reactive oxygen species production in response to conidia via PPP. In context to fungal pulmonary infections, our results show that Nlrx1 plays significant roles in host defense via PPP modulation of several aspects of metabolism, particularly glycolysis, to facilitate conidia processing in addition to its critical role in regulating immune signaling.

scholarly journals Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells

2005 ◽  
Vol 289 (5) ◽  
pp. L834-L841 ◽  
Author(s):  
Kenneth E. Chapman ◽  
Scott E. Sinclair ◽  
Daming Zhuang ◽  
Aviv Hassid ◽  
Leena P. Desai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Cell Line ◽  
Primary Cultures ◽  
Reactive Oxygen ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Ros Production ◽  
Oxygen Species ◽  
Type Ii

Overdistention of lung tissue during mechanical ventilation may be one of the factors that initiates ventilator-induced lung injury (VILI). We hypothesized that cyclic mechanical stretch (CMS) of the lung epithelium is involved in the early events of VILI through the production of reactive oxygen species (ROS). Cultures of an immortalized human airway epithelial cell line (16HBE), a human alveolar type II cell line (A549), and primary cultures of rat alveolar type II cells were cyclically stretched, and the production of superoxide (O2−) was measured by dihydroethidium fluorescence. CMS stimulated increased production of O2− after 2 h in each type of cell. 16HBE cells exhibited no significant stimulation of ROS before 2 h of CMS (20% strain, 30 cycles/min), and ROS production returned to control levels after 24 h. Oxidation of glutathione (GSH), a cellular antioxidant, increased with CMS as measured by a decrease in the ratio of the reduced GSH level to the oxidized GSH level. Strain levels of 10% did not increase O2− production in 16HBE cells, whereas 15, 20, and 30% significantly increased generation of O2−. Rotenone, a mitochondrial complex I inhibitor, partially abrogated the stretch-induced generation of O2− after 2 h CMS in 16HBE cells. NADPH oxidase activity was increased after 2 h of CMS, contributing to the production of O2−. Increased ROS production in lung epithelial cells in response to elevated stretch may contribute to the onset of VILI.

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