Reference - Detail
|Author||Kasakura K, Takahashi K, Aizawa T, Hosono A, Kaminogawa S.|
|Title||A TLR2 ligand suppresses allergic inflammatory reactions by acting directly on mast cells.|
|Journal||Int. Arch. Allergy Immunol.|
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 C(4) production triggered by engagement of the high-affinity IgE receptor, FcepsilonRI. Intracellular Ca(2+) mobilization and phosphorylation of Erk were suppressed by pretreatment with Pam3CSK4, suggesting that the TLR2 ligand suppresses activation of mast cells by interrupting FcepsilonRI-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 FcepsilonRI-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.
|MeSH||Animals Antigens, Bacterial / immunology Bifidobacterium / immunology* Capillary Permeability / drug effects Capillary Permeability / immunology Cell Degranulation / drug effects Cell Degranulation / immunology Cell Line Immunoglobulin E / immunology* Immunomodulation Lipopeptides / administration & dosage Lipopeptides / pharmacology* Mast Cells / drug effects Mast Cells / immunology Mast Cells / metabolism* Mast Cells / pathology Mice Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains Probiotics Receptors, IgE / immunology Receptors, IgE / metabolism Signal Transduction / drug effects Signal Transduction / immunology Toll-Like Receptor 2 / antagonists & inhibitors*|
|WOS Category||ALLERGY IMMUNOLOGY|
|General Microbes||JCM 7041|