Exposure to acrolein disrupts the molecular regulation of mitochondrial metabolism in epithelial cells of the human airways

2021 ◽  
Vol 350 ◽  
pp. S167-S168
Author(s):  
C. Tulen ◽  
C.H. Schiffers ◽  
C. van de Wetering ◽  
H.W. Cremers ◽  
E. Duistermaat ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mitochondrial Metabolism ◽  
Molecular Regulation ◽  
Human Airways

scholarly journals Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures

2008 ◽  
Vol 295 (1) ◽  
pp. L194-L200 ◽  
Author(s):  
Ashwini S. Sabnis ◽  
Christopher A. Reilly ◽  
John M. Veranth ◽  
Garold S. Yost
Keyword(s):  
Epithelial Cells ◽  
Human Lung ◽  
External Environment ◽  
Lung Epithelial Cells ◽  
Critical Element ◽  
Cold Temperatures ◽  
Cold Air ◽  
Lung Epithelial ◽  
Human Airways ◽  
Human Lung Epithelial Cells

Recognition of temperature is a critical element of sensory perception and allows mammals to evaluate both their external environment and internal status. The respiratory epithelium is constantly exposed to the external environment, and prolonged inhalation of cold air is detrimental to human airways. However, the mechanisms responsible for adverse effects elicited by cold air on the human airways are poorly understood. Transient receptor potential melastatin family member 8 (TRPM8) is a well-established cold- and menthol-sensing cation channel. We recently discovered a functional cold- and menthol-sensing variant of the TRPM8 ion channel in human lung epithelial cells. The present study explores the hypothesis that this TRPM8 variant mediates airway cell inflammatory responses elicited by cold air/temperatures. Here, we show that activation of the TRPM8 variant in human lung epithelial cells leads to increased expression of several cytokine and chemokine genes, including IL-1α, -1β, -4, -6, -8, and -13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α. Our results provide new insights into mechanisms that potentially control airway inflammation due to inhalation of cold air and suggest a possible role for the TRPM8 variant in the pathophysiology of asthma.

scholarly journals Tollip Inhibits ST2 Signaling in Airway Epithelial Cells Exposed to Type 2 Cytokines and Rhinovirus

2019 ◽  
Vol 12 (1) ◽  
pp. 103-115 ◽  
Author(s):  
Azzeddine Dakhama ◽  
Reem Al Mubarak ◽  
Nicole Pavelka ◽  
Dennis Voelker ◽  
Max Seibold ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Proinflammatory Response ◽  
Type 2 Cytokines ◽  
Cytokine Milieu ◽  
Human Airways

The negative immune regulator Tollip inhibits the proinflammatory response to rhinovirus (RV) infection, a contributor to airway neutrophilic inflammation and asthma exacerbations, but the underlying molecular mechanisms are poorly understood. Tollip may inhibit IRAK1, a signaling molecule downstream of ST2, the receptor of IL-33. This study was carried out to determine whether Tollip downregulates ST2 signaling via inhibition of IRAK1, but promotes soluble ST2 (sST2) production, thereby limiting excessive IL-8 production in human airway epithelial cells during RV infection in a type 2 cytokine milieu (e.g., IL-13 and IL-33 stimulation). Tollip- and IRAK1-deficient primary human tracheobronchial epithelial (HTBE) cells and Tollip knockout (KO) HTBE cells were generated using the shRNA knockdown and CRISPR/Cas9 approaches, respectively. Cells were stimulated with IL-13, IL-33, and/or RV16. sST2, activated IRAK1, and IL-8 were measured. A Tollip KO mouse model was utilized to test if Tollip regulates the airway inflammatory response to RV infection in vivo under IL-13 and IL-33 treatment. Following IL-13, IL-33, and RV treatment, Tollip-deficient (vs. -sufficient) HTBE cells produced excessive IL-8, accompanied by decreased sST2 production but increased IRAK1 activation. IL-8 production following IL-13/IL-33/RV exposure was markedly attenuated in IRAK1-deficient HTBE cells, as well as in Tollip KO HTBE cells treated with an IRAK1 inhibitor or a recombinant sST2 protein. Tollip KO (vs. wild-type) mice developed exaggerated airway neutrophilic responses to RV in the context of IL-13 and IL-33 treatment. Collectively, these data demonstrate that Tollip restricts excessive IL-8 production in type 2 cytokine-exposed human airways during RV infection by promoting sST2 production and inhibiting IRAK1 activation. sST2 and IRAK1 may be therapeutic targets for attenuating excessive neutrophilic airway inflammation in asthma, especially during RV infection.

scholarly journals Expression and localization of COX-2 in human airways and cultured airway epithelial cells

1999 ◽  
Vol 13 (5) ◽  
pp. 999 ◽  
Author(s):  
D.N. Watkins ◽  
D.J. Peroni ◽  
C. Lenzo ◽  
D.A. Knight ◽  
M.J. Garlepp ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cox 2 ◽  
Human Airways

scholarly journals Microscopic modeling of NO and S-nitrosoglutathione kinetics and transport in human airways

2001 ◽  
Vol 90 (3) ◽  
pp. 777-788 ◽  
Author(s):  
Hye-Won Shin ◽  
Steven C. George
Keyword(s):  
Steady State ◽  
Epithelial Cells ◽  
Inflammatory Diseases ◽  
Small Airways ◽  
Exhaled Breath ◽  
Exhaled No ◽  
Large Airways ◽  
Human Airways ◽  
Microscopic Modeling ◽  
Using Data

Nitric oxide (NO) appears in the exhaled breath and is elevated in inflammatory diseases. We developed a steady-state mathematical model of the bronchial mucosa for normal small and large airways to understand NO and S-nitrosoglutathione (GSNO) kinetics and transport using data from the existing literature. Our model predicts that mean steady-state NO and GSNO concentrations for large airways ( generation 1) are 2.68 nM and 113 pM, respectively, in the epithelial cells and 0.11 nM (∼66 ppb) and 507 nM in the mucus. For small airways ( generation 15), the mean concentrations of NO and GSNO, respectively, are 0.26 nM and 21 pM in the epithelial cells and 0.02 nM (∼12 ppb) and 132 nM in the mucus. The concentrations in the mucus compare favorably to experimentally measured values. We conclude that 1) the majority of free NO in the mucus, and thus exhaled NO, is due to diffusion of free NO from the epithelial cell and 2) the heterogeneous airway contribution to exhaled NO is due to heterogeneous airway geometries, such as epithelium and mucus thickness.

scholarly journals Autophagy as a double-edged sword in pulmonary epithelial injury: a review and perspective

2017 ◽  
Vol 313 (2) ◽  
pp. L207-L217 ◽  
Author(s):  
Zhou-Yang Li ◽  
Yin-Fang Wu ◽  
Xu-Chen Xu ◽  
Jie-Sen Zhou ◽  
Yong Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Developmental Changes ◽  
Airway Epithelial ◽  
First Line ◽  
Epithelial Injury ◽  
Pulmonary Epithelial Cells ◽  
Human Airways ◽  
Airway Epithelial Injury ◽  
Primary Injury

Pulmonary epithelial cells form the first line of defense of human airways against foreign irritants and also represent as the primary injury target of these pathogenic assaults. Autophagy is a revolutionary conserved ubiquitous process by which cytoplasmic materials are delivered to lysosomes for degradation when facing environmental and/or developmental changes, and emerging evidence suggests that autophagy plays pivotal but controversial roles in pulmonary epithelial injury. Here we review recent studies focusing on the roles of autophagy in regulating airway epithelial injury induced by various stimuli. Articles eligible for this purpose are divided into two groups according to the eventual roles of autophagy, either protective or deleterious. From the evidence summarized in this review, we draw several conclusions as follows: 1) in all cases when autophagy is decreased from its basal level, autophagy is protective; 2) when autophagy is deleterious, it is generally upregulated by stimulation; and 3) a plausible conclusion is that the endosomal/exosomal pathways may be associated with the deleterious function of autophagy in airway epithelial injury, although this needs to be clarified in future investigations.

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