scholarly journals STING Mediates Cytosolic Dna-Induced Muc5ac Mrna Expression in Human Bronchial Epithelial Cells

2020 ◽  
Author(s):  
Masaya Ohta ◽  
Yutaka Nishida ◽  
Hisako Yagi ◽  
Aikira Aizawa ◽  
Takahito Oyanagi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Cell Types ◽  
Bronchial Epithelial Cells ◽  
Epithelial Cell Line ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Dna Sensing ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

Abstract Background: Non-autologous and autologous cytosolic DNA are recognized as danger signals by cytoplasmic sensor molecules that activate signal-transduction pathways. An important molecule in cytosolic DNA sensing is stimulator of interferon genes (STING), an endoplasmic reticulum protein activated by cyclic GMP–AMP (cGAMP) produced in response to cytosolic DNA. STING is important for innate immune responses to cytosolic DNA in immune cells; however, knowledge about its role in bronchial epithelial cells is limited. Methods: We stimulated NCI-H292 cells with poly(dA:dT) and silenced STING and other regulatory proteins, and then determined MUC5AC mRNA expression levels. Results: Cytosolic DNA increased the expression of a major respiratory mucin protein, MUC5AC, in the human respiratory epithelial cell line NCI-H292 in a STING-dependent manner. Introducing poly(dA:dT) into the cytoplasm induced MUC5AC and interferon-β (IFNβ) expression. Silencing STING by RNA interference decreased poly(dA:dT)-induced MUC5AC mRNA expression but increased IFN-β mRNA levels. Furthermore, cGAMP treatment increased MUC5AC expression but not IFN-β expression. In contrast, silencing retinoic acid-inducible gene-I (RIG-I), which is a component of a different nucleic acid-sensing system, suppressed poly(dA:dT)-induced IFN-β expression and increased MUC5AC expression. Conclusions: Unlike its role in other cell types, in human bronchial epithelial cells, STING is central to cytosolic DNA-induced MUC5AC expression, whereas IFN-β expression is dependent on RIG-I. Our data indicate a functional interaction between the STING and RIG-I pathways, suggesting the existence of intricate and cell-specific cytosolic DNA-sensing systems.

scholarly journals Identification of abnormally expressed lncRNAs induced by PM2.5 in human bronchial epithelial cells

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Xing Li ◽  
Mengning Zheng ◽  
Jinding Pu ◽  
Yumin Zhou ◽  
Wei Hong ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Western Blot ◽  
Mrna Expression ◽  
Microarray Analysis ◽  
Cell Apoptosis ◽  
Expression Profiles ◽  
Bronchial Epithelial Cells ◽  
Dependent Manner ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

To investigate the effect of stimulation of human bronchial epithelial cells (HBECs) by arterial traffic ambient PM2.5 (TAPM2.5) and wood smoke PM2.5 (WSPM2.5) on the expression of long non-coding RNAs (lncRNAs) in order to find new therapeutic targets for treatment of chronic obstructive pulmonary disease (COPD). HBECs were exposed to TAPM2.5 and WSPM2.5 at a series of concentrations. The microarray analysis was used to detect the lncRNA and mRNA expression profiles. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene ontology (GO) enrichment were conducted to analyze the differentially expressed lncRNAs and mRNAs. Quantitative real-time PCR (qRT-PCR) was performed to confirm the differential expression of lncRNAs. Western blot was performed to study the expression of autophagy and apoptosis-associated proteins. Flow cytometry was used to detect the apoptotic cells. The results indicated that fine particulate matter (PM2.5)-induced cell damage of HBECs occurred in a dose-dependent manner. The microarray analysis indicated that treatment with TAPM2.5 and WSPM2.5 led to the alteration of lncRNA and mRNA expression profiles. LncRNA maternally expressed gene 3 (MEG3) was significantly up-regulated in HBECs after PM2.5 treatment. The results of Western blot showed that PM2.5 induced cell apoptosis and autophagy by up-regulating apoptosis-associated gene, caspase-3, and down-regulating autophagy-associated markers, Bcl-2 and LC3 expression. In addition, we demonstrated that TAPM2.5 and WSPM2.5 accelerated apoptosis of human bronchial (HBE) cells, silencing of MEG3 suppressed apoptosis and autophagy of HBE cells. These findings suggested that the lncRNA MEG3 mediates PM2.5-induced cell apoptosis and autophagy, and probably through regulating the expression of p53.

Aspergillus Fumigatus Extract Suppresses the mRNA Expression of the IP-10 in Human Bronchial Epithelial Cells

2014 ◽  
Vol 151 (1_suppl) ◽  
pp. P248-P248
Author(s):  
Bharat Bhushan ◽  
James E. Norton ◽  
Dave Gupta ◽  
Quen Sha ◽  
James W. Schroeder ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Aspergillus Fumigatus ◽  
Mrna Expression ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

scholarly journals Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation

2019 ◽  
Vol 316 (1) ◽  
pp. L245-L254 ◽  
Author(s):  
Yuqing Mo ◽  
Kan Zhang ◽  
Yuchen Feng ◽  
Lingling Yi ◽  
Yuxia Liang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Murine Model ◽  
Allergic Airway Inflammation ◽  
Bronchial Epithelial Cells ◽  
Mrna Levels ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Airway Eosinophilia

Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in an animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR) and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN, and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.

Induction of MMP-9 in normal human bronchial epithelial cells by TNF-α via NF-κB-mediated pathway

2001 ◽  
Vol 281 (6) ◽  
pp. L1444-L1452 ◽  
Author(s):  
Atsuko Hozumi ◽  
Yoshihiro Nishimura ◽  
Teruaki Nishiuma ◽  
Yoshikazu Kotani ◽  
Mitsuhiro Yokoyama
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Interleukin 1Β ◽  
Pyrrolidine Dithiocarbamate ◽  
Mrna Levels ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Tnf Α ◽  
Normal Human

In this study, we determined whether the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin-1β contribute to the regulation of matrix metalloproteinase (MMP)-9 in human bronchial epithelial cells and whether the induction of MMP-9 is regulated by the transcription factor nuclear factor (NF)-κB. We demonstrated that TNF-α induced MMP-9 at both the protein and mRNA levels in human bronchial epithelial cells and that interleukin-1β did not. In contrast, induction of the tissue inhibitor of metalloproteinase-1 by TNF-α was less than that of interleukin-1β. Increased expression of MMP-9 and NF-κB activation induced by TNF-α were inhibited by pyrrolidine dithiocarbamate and N-acetyl-l-cysteine but were not inhibited by curcumin. These results suggest that TNF-α induces the expression of MMP-9 in human bronchial epithelial cells and that this induction is mediated via the NF-κB-mediated pathway.

Feedlot dust stimulation of interleukin-6 and -8 requires protein kinase Cε in human bronchial epithelial cells

2007 ◽  
Vol 293 (5) ◽  
pp. L1163-L1170 ◽  
Author(s):  
Todd A. Wyatt ◽  
Rebecca E. Slager ◽  
Jane DeVasure ◽  
Brent W. Auvermann ◽  
Michael L. Mulhern ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Cell Line ◽  
Bronchial Epithelial Cells ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Dust Extract

Individuals exposed to dusts from concentrated animal feeding operations report increased numbers of respiratory tract symptoms, and bronchoalveolar lavage samples from such individuals demonstrate elevated lung inflammatory mediators, including interleukin (IL)-8 and IL-6. We previously found that exposure of bronchial epithelial cells to hog barn dusts resulted in a protein kinase C (PKC)-dependent increase in IL-6 and IL-8 release. We hypothesized that cattle feedlot dusts would also generate bronchial epithelial interleukin release in vitro. To test this, we used interleukin ELISAs and direct PKC isoform assays. We found that a dust extract from cattle feedlots [feedlot dust extract (FLDE)] augments PKC activity of human bronchial epithelial cells in vitro. A 5–10% dilution of FLDE stimulated a significant release of IL-6 and IL-8 at 6–24 h in a PKC-dependent manner vs. control medium-treated cells. An increase in PKCα activity was observed with 1 h of FLDE treatment, and PKCε activity was elevated at 6 h of FLDE exposure. The PKCα inhibitor, Gö-6976, did not inhibit FLDE-stimulated IL-8 and IL-6 release. However, the PKCε inhibitor, Ro 31-8220, effectively inhibited FLDE-stimulated IL-8 and IL-6 release. Inhibition of FLDE-stimulated IL-6 and IL-8 was confirmed in a dominant-negative PKCε-expressing BEAS-2B cell line but not observed in a PKCα dominant negative BEAS-2B cell line. These data support the hypothesis that FLDE exposure stimulates bronchial epithelial IL-8 and IL-6 release via a PKCε-dependent pathway.

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