title: Synergistic augmentation of inflammatory cytokine productions from murine mast cells by monomeric IgE and toll-like receptor ligands.
abstract: Simultaneous activation of murine mast cells by monomeric IgE and toll-like receptor (TLR) ligands was examined. Inflammatory cytokine production elicited by the binding of IgE in the absence of antigen, was further enhanced by the addition of lipopolysaccharide (LPS) or peptidoglycan (PGN). Enhancement by LPS or PGN on cytokine production was mediated by TLR4 and TLR2, respectively, since TLR4- and TLR2-deficient mast cells did not show synergistic activation by monomeric IgE and LPS/PGN. Synergistic activation of mast cells was obtained via phosphorylation of several mitogen-activated protein kinases (MAPK). Furthermore, MAPK inhibitors, significantly attenuated the augmentation of inflammatory cytokine production by monomeric IgE and LPS or PGN. Altogether, these results suggest that simultaneous TLR activation of mast cells with IgE molecules, particularly highly cytokinergic (HC) IgE, might contribute to the exacerbation of allergic diseases associated with infection even in the absence of a specific antigen.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takenaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ushio
authors.forename: François
authors.initials: F
authors.lastname: Niyonsaba
authors.forename: Sumanasiri T M
authors.initials: ST
authors.lastname: Jayawardana
authors.forename: Suto
authors.initials: S
authors.lastname: Hajime
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D007073:Immunoglobulin E / Q000276:immunology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D007073:Immunoglobulin E; D020929:Mitogen-Activated Protein Kinase Kinases