Original Paper

A TLR2 Ligand Suppresses Allergic Inflammatory Reactions by Acting Directly on Mast Cells
Kazumi Kasakura, Kyoko Takahashi, Tomoyuki Aizawa, Akira Hosono, Shuichi Kaminogawa

Laboratory of Biological Chemistry on Food Functionalities, Department of Food Science and Technology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan

Address of Corresponding Author

Int Arch Allergy Immunol 2009;150:359-369 (DOI: 10.1159/000226237)

  Key Words

• Mast cell
• Toll-like receptor
• Probiotic
• Bifidobacterium
• Degranulation
• Cytokine
• Leukotriene
• Vascular permeability
• Intracellular signal

  Abstract

Background: Although much attention has been focused on the anti-allergic effects of probiotics, their mode of action is not fully understood. Mast cells, which play a central role in inducing allergic inflammation, are potential targets of probiotics given the recent discovery that they express Toll-like receptors (TLRs), the pattern recognition receptors for microbial components. In this study, we examined whether allergic reactions of mast cells are modulated by stimulation through TLR2. Methods: The effects on mast cells of the synthetic TLR2 ligand Pam3CSK4 and Bifidobacterium pseudocatenulatum JCM 7041 were evaluated in vitro. Furthermore, the effects of Pam3CSK4 on mast cell-induced increase in vascular permeability in vivo were investigated by employing mast cell-deficient W/W^v mice into which IgE-sensitized mouse bone marrow-derived mast cells were transferred. Results: Pam3CSK4 and Bifidobacterium pseudocatenulatum JCM 7041 suppressed degranulation of IgE-sensitized mast cells upon antigen stimulation in vitro. Pam3CSK4 also suppressed leukotriene C₄ production triggered by engagement of the high-affinity IgE receptor, FcεRI. Intracellular Ca²⁺ mobilization and phosphorylation of Erk were suppressed by pretreatment with Pam3CSK4, suggesting that the TLR2 ligand suppresses activation of mast cells by interrupting FcεRI-mediated intracellular signaling. Pam3CSK4 treatment of bone marrow-derived mast cells reduced the increase in vascular permeability in recipient W/W^v mice upon intravenous injection of antigen; the decrease was by about half, in a TLR-dependent manner. Conclusion: Collectively, these results demonstrate that the FcεRI-mediated inflammatory responses of mast cells are suppressed by stimulation through TLR2, suggesting that probiotics exert potential anti-allergic effects, at least in part, through direct effects on mast cells.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. Kyoko Takahashi
Laboratory of Biological Chemistry on Food Functionalities
Department of Food Science and Technology, College of Bioresource Sciences
Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-8510 (Japan)
Tel. +81 466 84 3985, Fax +81 466 84 3984, E-Mail ktaka@brs.nihon-u.ac.jp

  Article Information

Received: July 18, 2008
Accepted after revision: March 25, 2009
Published online: July 1, 2009
Number of Print Pages : 11
Number of Figures : 6, Number of Tables : 0, Number of References : 31