The TLR4-associated phospholipase D1 activation is crucial for Der f 2-induced IL-13 production

Allergy
Hye-Jin ChoiJoong-Soo Han

Abstract

House dust mites (HDMs) are the most important source of indoor aeroallergens that contribute to the rising incidence of allergic diseases such as allergic asthma. The major HDM, Der f 2, induces inflammatory cytokine expression. Little is known about the signaling pathway involved. We wanted to define the Der f 2 signaling pathway from its receptor to the transcription factor responsible for IL-13 expression and production. Human bronchial epithelial cells were stimulated with Der f 2. The release and gene expression of IL-13 were measured by means of ELISA and RT-PCR, respectively. In the airway inflammation mouse model, airway responses were assessed using ELISA, histology, BAL fluid, and methacholine responsiveness. Here, we show that Der f 2 binds to TLR4 and induces IL-13 expression and production. In the airway inflammation mouse model, Der f 2-induced IL-13 production significantly decreased with treatment of TAK-242, a novel TLR4 inhibitor. Activation of TLR4 by Der f 2 requires the recruitment and activation of Syk, which leads to phosphorylation of PLCγ and membrane translocation of PKCα. p38 MAPK is then activated by PKCα and stimulates PLD1 activity by phosphorylating the Thr147 residue of PLD1. PLD1 activation enh...Continue Reading

References

May 1, 1988·The Journal of Allergy and Clinical Immunology·J S van der ZeeR C Aalberse
Jun 1, 1989·The Journal of Allergy and Clinical Immunology·P W HeymannT A Platts-Mills
May 24, 1996·Chemistry and Physics of Lipids·V Natarajan
Jul 9, 1998·Molecular and Cellular Biochemistry·V NatarajanW M Scribner
Jul 30, 1999·Biochimica Et Biophysica Acta·J H Exton
Sep 4, 2001·Current Pharmaceutical Biotechnology·P M Steed, A H Chow
Feb 28, 2002·Annual Review of Immunology·Charles A Janeway, Ruslan Medzhitov
Apr 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karim DabbaghDavid B Lewis
Feb 14, 2003·American Journal of Physiology. Cell Physiology·Dezheng ZhaoCharalabos Pothoulakis
Jun 7, 2003·Science·Gregory M Barton, Ruslan Medzhitov
Jul 2, 2004·Nature Reviews. Immunology·Shizuo Akira, Kiyoshi Takeda
Mar 16, 2005·The Lancet Infectious Diseases·Nicolas W J Schröder, Ralf R Schumann
Dec 27, 2005·Cellular Signalling·Saradhadevi VaradharajNarasimham L Parinandi
Jan 18, 2007·Immunology and Cell Biology·Anu ChaudharyMichele J Naranjo
Aug 22, 2007·The British Journal of Radiology·V HaydontM-C Vozenin-Brotons
Dec 28, 2007·Journal of Leukocyte Biology·Steven C GribarDavid J Hackam
Aug 15, 2009·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Saori IchikawaHideki Hatanaka
Apr 9, 2011·The Journal of Pharmacology and Experimental Therapeutics·Jeong Woo ParkSoo Wan Kim

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