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
Open Access
- 24 July 2009
- journal article
- Published by Elsevier BV
- Vol. 284 (30), 20099-20110
- https://doi.org/10.1074/jbc.m109.010017
Abstract
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 Cgamma (PLCgamma)/protein kinase Calpha (PKCalpha)/p38 MAPK pathway. Der f 2-induced PLD activation was attenuated by PLCgamma inhibitors (U73122 and PAO), PKCalpha inhibitors (RO320432 and GO6976), and p38 MAPK inhibitors (SB203580 and SB202190). These results indicate that PLCgamma, PKCalpha, 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 PLCgamma, PKCalpha, or p38 MAPK, indicating that IL-13 expression and production are related to a PLCgamma/PKCalpha/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.Keywords
This publication has 70 references indexed in Scilit:
- Human adenovirus type 19 infection of corneal cells induces p38 MAPK-dependent interleukin-8 expressionVirology Journal, 2008
- Phospholipase D1 activation through Src and Ras is involved in basic fibroblast growth factor‐induced neurite outgrowth of H19‐7 cellsJournal of Cellular Biochemistry, 2006
- Regulation of TNF mediated antiapoptotic signaling in human neutrophils: role of δ-PKC and ERK1/2Journal of Leukocyte Biology, 2006
- Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves γ-globin activation by CREB1 and ATF-2Blood, 2006
- Activation and signaling of the p38 MAP kinase pathwayCell Research, 2005
- Der f 2 activates phospholipase D in human T lymphocytes from Dermatophagoides farinae specific allergic individuals: Involvement of protein kinase C-αExperimental & Molecular Medicine, 2004
- Phospholipase C, protein kinase C, Ca2+/calmodulin‐dependent protein kinase II, and redox state are involved in epigallocatechin gallate‐induced phospholipase D activation in human astroglioma cellsEuropean Journal of Biochemistry, 2004
- PKC-ζ Mediates Norepinephrine-Induced Phospholipase D Activation and Cell Proliferation in VSMCHypertension, 2003
- Major house dust mite allergen, Der p I, activates phospholipase D in human peripheral blood mononuclear cells from allergic patients: involvement of protein kinase CExperimental & Molecular Medicine, 2000
- SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin‐1FEBS Letters, 1995