PLD1 activation mediates Amb a 1-induced Th2-associated cytokine expression via the JNK/ATF-2 pathway in BEAS-2B cells

• Published in: Cellular immunology 2015-11, Vol.298 (1-2), p.9-17
• Main Authors: Kim, Joo-Hwa, Choi, Hye-Jin, Oh, Cheong-Hae, Oh, Jae-Won, Han, Joong-Soo
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 2 - genetics; Ambrosia artemisiifolia; Antigens, Plant - immunology; Cell Line, Transformed; Enzyme Activation; Humans; IL-13; IL-5; Interleukin-13 - biosynthesis; Interleukin-5 - biosynthesis; JNK; JNK Mitogen-Activated Protein Kinases - immunology; MAP Kinase Signaling System - immunology; p70S6K; Phospholipase C gamma - antagonists & inhibitors; Phospholipase C gamma - immunology; Phospholipase D - genetics; Phospholipase D - metabolism; Plant Proteins - immunology; PLD1; Ribosomal Protein S6 Kinases, 70-kDa - immunology; RNA Interference; RNA, Small Interfering; Th2 Cells - immunology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2015.08.003

•PLD1 is involved in Amb a 1-induced IL-5 and IL-13 expression in BEAS-2B cells.•Amb a 1-induces IL-5 and IL-13 expression through PLCγ/PLD1/p70S6K pathway.•JNK activation is important for Amb a 1-induced IL-5 and IL-13 expression.•JNK activates ATF-2, which acts as a transcription factor for IL-5 and IL-13 expression. The purpose of this study was to identify the role of phospholipase D1 (PLD1) in Amb a 1-induced IL-5 and IL-13 expression. When BEAS-2B cells were stimulated with Amb a 1, PLD activity increased, and knockdown of PLD1 decreased Amb a 1-induced IL-5 and IL-13 expression. Amb a 1 also activated the PLCγ/p70S6K/JNK pathway. Furthermore, Amb a 1-induced PLD activation was also attenuated by PLCγ inhibition, and knockdown of PLD1 decreased Amb a 1-induced activation of P70S6K and JNK. When ATF-2 activity was blocked with ATF-2 siRNA, Amb a 1-induced IL-5 and IL-13 expression was completely abolished, indicating that ATF-2 is a transcriptional factor required for the expression of IL-5 and IL-13 in response to Amb a 1. Taken together, we suggest that PLD1 acts as an important regulator in Amb a 1-induced expression of IL-5 and IL-13 via a PLCγ/p70S6K/JNK/ATF-2 pathway in BEAS-2B cells.