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

• Published in: The Journal of biological chemistry Vol. 284; no. 30; pp. 20099 - 20110
• Main Authors: Park, Shin-Young, Cho, Ju Hwan, Oh, Doo-Yi, Park, Jung-Won, Ahn, Myung-Ju, Han, Joong-Soo, Oh, Jae-Won
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.07.2009; American Society for Biochemistry and Molecular Biology
• Subjects: Activating Transcription Factor 2 - genetics; Activating Transcription Factor 2 - immunology; Activating Transcription Factor 2 - metabolism; Antigens, Dermatophagoides - immunology; Arthropod Proteins; Bronchi - cytology; Cell Line, Transformed; Enzyme Activation; Epithelial Cells - cytology; Epithelial Cells - immunology; Gene Expression Regulation; Humans; Interleukin-13 - genetics; Interleukin-13 - immunology; Mechanisms of Signal Transduction; p38 Mitogen-Activated Protein Kinases - immunology; p38 Mitogen-Activated Protein Kinases - metabolism; Phospholipase C gamma - immunology; Phospholipase C gamma - metabolism; Phospholipase D - immunology; Phospholipase D - metabolism; Protein Kinase C-alpha - immunology; Protein Kinase C-alpha - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.010017

The purpose of this study was to identify the role of phospholipase D1 (PLD1) in Der 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 Cγ (PLCγ)/protein kinase Cα (PKCα)/p38 MAPK pathway. Der f 2-induced PLD activation was attenuated by PLCγ inhibitors (U73122 and PAO), PKCα inhibitors (RO320432 and GO6976), and p38 MAPK inhibitors (SB203580 and SB202190). These results indicate that PLCγ, PKCα, 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 PLCγ, PKCα, or p38 MAPK, indicating that IL-13 expression and production are related to a PLCγ/PKCα/p38 MAPK pathway. We found that activating transcription factor-2 (ATF-2) was activated by Der 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 in Der 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.