Differential effects of the Toll-like receptor 2 agonists, PGN and Pam3CSK4 on anti-IgE induced human mast cell activation.
Mast cells are pivotal in the pathogenesis of allergy and inflammation. In addition to the classical IgE-dependent mechanism involving crosslinking of the high-affinity receptor for IgE (FcεRI), mast cells are also activated by Toll-like receptors (TLRs) which are at the center of innate immunity. In this study, we demonstrated that the response of LAD2 cells (a human mast cell line) to anti-IgE was altered in the presence of the TLR2 agonists peptidoglycan (PGN) and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4). Pretreatment of PGN and Pam3CSK4 inhibited anti-IgE induced calcium mobilization and degranulation without down-regulation of FcεRI expression. Pam3CSK4 but not PGN acted in synergy with anti-IgE for IL-8 release when the TLR2 agonist was added simultaneously with anti-IgE. Studies with inhibitors of key enzymes implicated in mast cell signaling revealed that the synergistic release of IL-8 induced by Pam3CSK4 and anti-IgE involved ERK and calcineurin signaling cascades. The differential modulations of anti-IgE induced mast cell activation by PGN and Pam3CSK4 suggest that dimerization of TLR2 with TLR1 or TLR6 produced different modulating actions on FcεRI mediated human mast cell activation.
Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, China; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Yangyang
Y
Yu
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Kwok Ho
KH
Yip
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Issan Yee San
IY
Tam
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Sze Wing
SW
Sam
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Chun Wai
CW
Ng
Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, China.
Wei
W
Zhang
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Hang Yung Alaster
HY
Lau
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D019703:Calcineurin / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology*; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D016209:Interleukin-8; D008024:Ligands; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D010457:Peptidoglycan; D017455:Receptors, IgE; D051195:Toll-Like Receptor 2; C026408:anti-IgE antibodies; D048049:Extracellular Signal-Regulated MAP Kinases; D019703:Calcineurin; D002118:Calcium