The House Dust Mite Allergen Derf 2-induced Phospholipase D1 Activation Is Critical for the Production of Interleukin-13 through Activating Transcription Factor-2 Activation in Human Bronchial Epithelial Cells

Abstract

The purpose of this study was to identify the role of phospholipase D1 (PLD1) inDer f 2-induced interleukin (IL)-13 production. The major house dust mite allergen,Der f 2, increased PLD activity in human bronchial epithelial cells (BEAS-2B), and dominant negative PLD1 or PLD1 siRNA decreased Der f 2-induced IL-13 expression and production. Treatment of Der f 2 activated the phospholipase C (PLC)/protein kinase C (PKC)/p38 MAPK pathway. Der f 2-induced PLD activation was attenuated by PLC inhibitors (U73122 and PAO), PKC inhibitors (RO320432 and GO6976), and p38 MAPK inhibitors (SB203580 and SB202190). These results indicate that PLC, PKC, and p38 MAPK act as upstream activators of PLD in Der f 2-treated BEAS-2B cells. Furthermore, expression and production of IL-13 increased by Der f 2 were also blocked by inhibition of PLC, PKC, or p38 MAPK, indicating that IL-13 expression and production are related to a PLC/PKC/p38 MAPKpathway.Wefound that activating transcription factor-2 (ATF-2) was activated byDer f 2 in BEAS-2B cells and activation of ATF-2 was controlled by PLD1. When ATF-2 activity was blocked with ATF-2 siRNA, Der f 2-induced IL-13 expression and production were decreased. Thus, ATF-2 might be one of the transcriptional factors for the expression of IL-13 inDer f 2- treated BEAS-2B cells. Taken together, PLD1 acts as an important regulator in Der f 2-induced expression and production of IL-13 through activation of ATF-2 in BEAS-2B cells.