Differential effects of the Toll-like receptor 2 agonists, PGN and Pam3CSK4 on anti-IgE induced human mast cell activation.

Abstract

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.

• Authors: Yangyang Yu, Kwok Ho Yip, Issan Yee San Tam, Sze Wing Sam, Chun Wai Ng, Wei Zhang, Hang Yung Alaster Lau
• Journal: PloS one (PLoS One) Vol. 9 Issue 11 Pg. e112989 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25398056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Interleukin-8
• Ligands
• Lipopeptides
• Pam(3)CSK(4) peptide
• Peptidoglycan
• Receptors, IgE
• Toll-Like Receptor 2
• anti-IgE antibodies
• Extracellular Signal-Regulated MAP Kinases
• Calcineurin
• Calcium

Topics

• Antibodies, Anti-Idiotypic (pharmacology)
• Calcineurin (chemistry, metabolism)
• Calcium (metabolism)
• Cell Degranulation (drug effects)
• Cell Line
• Down-Regulation (drug effects)
• Drug Synergism
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Flow Cytometry
• Humans
• Immunity, Innate
• Interleukin-8 (metabolism)
• Ligands
• Lipopeptides (pharmacology)
• Mast Cells (cytology, drug effects, metabolism)
• Peptidoglycan (pharmacology)
• Receptors, IgE (metabolism)
• Signal Transduction (drug effects)
• Toll-Like Receptor 2 (agonists, metabolism)