Home
|
Inbox
|
Search
|
View Abstract
Diesel Exhaust Particles (DEP) Induced Epithelium-Derived Cytokines Expression in Severe Allergic Asthma Through Aryl Hydrocarbon Receptor (AhR) Activation
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A2481 - Diesel Exhaust Particles (DEP) Induced Epithelium-Derived Cytokines Expression in Severe Allergic Asthma Through Aryl Hydrocarbon Receptor (AhR) Activation
Author Block: C. Weng1, C. Wang2, M. Lee1, H. Kuo2; 1Department of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan, 2Chang Gung Memorial Hosp, Taipei, Taiwan.
Exposure to airborne pollutants, such as DEP, has been associated with asthma exacerbations by enhancing Th2 responses with up-regulated IgE production. AhR activation mediates airway inflammation, enhances IgE production and aggravates allergic diseases. Epithelium-derived cytokines, TSLP, IL-25 and IL-33 are involved in pathogenesis of severe allergic asthma. In this study, we examined whether DEP activation of AhR led to TSLP, IL-25 and IL-33 expression in primary bronchial epithelial cells obtained from uncontrolled severe allergic asthmatics. DEP concentration-dependently increased IL-33, IL-25 and TSLP mRNA expression, protein expression and release. Transfection with AhR siRNA dramatically inhibited DEP-induced IL-33, IL-25 and TSLP mRNA expression, protein expression and release. Furthermore, DEP induced AhR nuclear translocation (NT). ChIP assay revealed that DEP induced a prominent increase in AhR binding to IL-33, IL-25 and TSLP promoter sites, which accompanied with an increase in Rel B binding, but not p65. DEP also increased the transcriptional activity of IL-33, IL-25 and TSLP promoters. DEP induced increase of ROS and NF-κB activation. Pretreatment with N-acetylcysteine (NAC) attenuated DEP-induced cytokines mRNA expression and NF-κB activation. Pretreatment with SN50, a NF-κB inhibitory peptide, completely inhibited DEP-induced IL-33, IL-25 and TSLP mRNA expression. In summary, DEP activates AhR and NF-κB through ROS production, leading to recruitment of AhR/Rel B complex to IL-33, IL-25 and TSLP promoters, and up-regulates these gene expression. Our results demonstrated a possible mechanism of epithelium-derived cytokines expression induced by DEP, and provide a linkage between environmental pollution and severe allergic asthma.
Author Block: C. Weng1, C. Wang2, M. Lee1, H. Kuo2; 1Department of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan, 2Chang Gung Memorial Hosp, Taipei, Taiwan.
Exposure to airborne pollutants, such as DEP, has been associated with asthma exacerbations by enhancing Th2 responses with up-regulated IgE production. AhR activation mediates airway inflammation, enhances IgE production and aggravates allergic diseases. Epithelium-derived cytokines, TSLP, IL-25 and IL-33 are involved in pathogenesis of severe allergic asthma. In this study, we examined whether DEP activation of AhR led to TSLP, IL-25 and IL-33 expression in primary bronchial epithelial cells obtained from uncontrolled severe allergic asthmatics. DEP concentration-dependently increased IL-33, IL-25 and TSLP mRNA expression, protein expression and release. Transfection with AhR siRNA dramatically inhibited DEP-induced IL-33, IL-25 and TSLP mRNA expression, protein expression and release. Furthermore, DEP induced AhR nuclear translocation (NT). ChIP assay revealed that DEP induced a prominent increase in AhR binding to IL-33, IL-25 and TSLP promoter sites, which accompanied with an increase in Rel B binding, but not p65. DEP also increased the transcriptional activity of IL-33, IL-25 and TSLP promoters. DEP induced increase of ROS and NF-κB activation. Pretreatment with N-acetylcysteine (NAC) attenuated DEP-induced cytokines mRNA expression and NF-κB activation. Pretreatment with SN50, a NF-κB inhibitory peptide, completely inhibited DEP-induced IL-33, IL-25 and TSLP mRNA expression. In summary, DEP activates AhR and NF-κB through ROS production, leading to recruitment of AhR/Rel B complex to IL-33, IL-25 and TSLP promoters, and up-regulates these gene expression. Our results demonstrated a possible mechanism of epithelium-derived cytokines expression induced by DEP, and provide a linkage between environmental pollution and severe allergic asthma.
|
Home
|
Inbox
|
Search
|