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). And many diseases occurred by cigarette smoking are related to interleukin-6(IL-6). In this study, we investigated the role of phospholipase D1 (PLD1) in IL-6 expression induced by cigarette smoke extract (CSE). CSE increased PLD1 and IL-6 expression in human bronchial epithelial cells (Beas-2B). CSE treatment activated PLC/PKC/p38MAPK pathway through Gi protein coupled receptor. CSE�induced PLD1 expression was decreased by pertussis toxin (PTX, Gi protein coupled receptor inhibitor), PAO (PLC inhibitor), Go6976 (PKC inhibitor) and SB203580 (p38MAPK inhibitor), respectively. These 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. Also, inhibitors of Gi protein, PLC, and PKC pretreatment and ATF2 siRNA transfection decreased CSE-induced IL-6 expression, suggesting that CSE-induced IL-6 expression is regulated by through Gi protein/PLC/PKC/p38MAPK/PLD1/ATF2 pathway. Taken together, PLD1 acts as an important regulator in IL-6 expression induced by CSE in Beas-2B cells.