title: The Effect of Therapeutic Blockades of Dust Particles-Induced Ca²⁺ Signaling and Proinflammatory Cytokine IL-8 in Human Bronchial Epithelial Cells.
abstract: Bronchial epithelial cells are the first barrier of defense against respiratory pathogens. Dust particles as extracellular stimuli are associated with inflammatory reactions after inhalation. It has been reported that dust particles induce intracellular Ca(2+) signal, which subsequently increases cytokines production such as interleukin- (IL-) 8. However, the study of therapeutic blockades of Ca(2+) signaling induced by dust particles in human bronchial epithelial cells is poorly understood. We investigated how to modulate dust particles-induced Ca(2+) signaling and proinflammatory cytokine IL-8 expression. Bronchial epithelial BEAS-2B cells were exposed to PM10 dust particles and subsequent mediated intracellular Ca(2+) signaling and reactive oxygen species signal. Our results show that exposure to several inhibitors of Ca(2+) pathway attenuated the PM10-induced Ca(2+) response and subsequent IL-8 mRNA expression. PM10-mediated Ca(2+) signal and IL-8 expression were attenuated by several pharmacological blockades such as antioxidants, IP3-PLC blockers, and TRPM2 inhibitors. Our results show that blockades of PLC or TRPM2 reduced both of PM10-mediated Ca(2+) signal and IL-8 expression, suggesting that treatment with these blockades should be considered for potential therapeutic trials in pulmonary epithelium for inflammation caused by environmental events such as seasonal dust storm.
authors.affiliation: Department of Physiology, Graduate School of Medicine, Gachon University, 191 Hambakmeoro, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Gachon University, Gil Medical Center, Incheon 405-706, Republic of Korea.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Physiology, Graduate School of Medicine, Gachon University, 191 Hambakmeoro, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D004391:Dust / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000276:immunology / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050053:TRPM Cation Channels / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000975:Antioxidants; C508606:CXCL8 protein, human; D004391:Dust; D016209:Interleukin-8; D052638:Particulate Matter; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases