Progress in allergy signal research on mast cells: regulation of allergic airway inflammation through toll-like receptor 4-mediated modification of mast cell function.
In a mouse experimental asthma model, the administration of bacterial lipopolysaccharide (LPS), particularly at low doses, enhances the levels of ovalbumin (OVA)-induced eosinophilic airway inflammation. In an effort to clarify the cellular and molecular basis for the LPS effect, we demonstrate that the OVA-induced eosinophilic inflammation in the lung is dramatically increased by administration of LPS at the priming phase in wild-type mice, whereas such an increase was not observed in mast cell deficient mice. Adoptive transfer of bone marrow-derived mast cells (BMMC) from wild type but not from Toll-like receptor 4 (TLR4)-deficient mice restored the increased eosinophilic inflammation in mast cell-deficient mice. Moreover, in vitro analysis revealed that treatment of BMMC with LPS resulted in sustained up-regulation of GATA1 expression and increased production of Th2 cytokines (IL-4, IL-5, and IL-13) upon restimulation. Thus, mast cells appear to control allergic airway inflammation after their activation and modulation through TLR4-mediated induction of GATA1 proteins and subsequent increase in Th2 cytokine production.
Yamashita
Masakatsu
M
Department of Immunology, Graduate School of Medicine, Chiba University, Japan. yamamasa@faculty.chiba-u.jp
Nakayama
Toshinori
T
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000209:etiology*; D016207:Cytokines / Q000096:biosynthesis; D004802:Eosinophilia / Q000209:etiology; D050982:GATA1 Transcription Factor / Q000235:genetics; D050989:GATA2 Transcription Factor / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000502:physiology*
D016207:Cytokines; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4