title: Cigarette smoke extract-induced interleukin-6 expression is regulated by phospholipase D1 in human bronchial epithelial cells.
abstract: Cigarette smoking is known to be associated with various kinds of diseases, including atherosclerotic cardiovascular disease, cancer, and chronic obstructive pulmonary disease (COPD). Many of the diseases associated with cigarette smoking are also associated with changes in interleukin-6 (IL-6) expression. In this study, we investigated the role of phospholipase D1 (PLD1) in IL-6 expression induced by cigarette smoke extract (CSE). Treatment with CSE increased PLD1 and IL-6 expressions in human bronchial epithelial (BEAS-2B) cells. In addition, CSE treatment activated PLC, PKC, and MAPK pathway through the Gi protein-coupled receptor. Pertussis toxin (PTX, Gi protein-coupled receptor inhibitor), PAO (PLC inhibitor), Go6976 (PKC inhibitor) and SB203580 (p38MAPK inhibitor) decreased CSE-induced PLD1 expression. The results show that Gi protein, PLC, PKC, and p38MAPK act as upstream regulators of PLD1 in CSE-treated BEAS-2B cells. Moreover, PLD1 siRNA transfection decreased CSE-induced ATF2 phosphorylation and IL-6 expression. In addition, inhibitors of Gi protein, PLC, PKC, and p38MAPK, and ATF2 siRNA transfection decreased CSE-induced IL-6 expression, suggesting that CSE-induced IL-6 expression is regulated via Gi protein/PLC/PKC/p38MAPK/PLD1/ATF2 pathway. Taken together, the results suggest that PLD1 is an important regulator of IL-6 expression induced by CSE in BEAS-2B cells.
authors.affiliation: Biomedical Research Institute and Department of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, Korea.
authors.forename: Jun Bon
authors.initials: JB
authors.lastname: Koo
authors.forename: Joong-Soo
authors.initials: JS
authors.lastname: Han
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology*; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D062789:Tobacco Products / Q000009:adverse effects*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012906:Smoke; D010739:Phospholipase D; C106801:phospholipase D1