Document Detail

Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function.
MedLine Citation:
PMID:  16461458     Owner:  NLM     Status:  MEDLINE    
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 the administration of LPS in wild-type mice, whereas such increase was not observed in mast-cell-deficient mice or Toll-like receptor (TLR)4-deficient mice. Adoptive transfer of bone-marrow-derived mast cells (BMMCs) from wild-type, but not from TLR4-deficient, mice restored the increased eosinophilic inflammation in mast-cell-deficient mice. Wild-type BMMCs pretreated with LPS in vitro also reconstituted the eosinophilic inflammation. Moreover, in vitro analysis revealed that the treatment of BMMCs with LPS resulted in NF-kappaB activation, sustained up-regulation of GATA1 and -2 expression, and increased the capability to produce IL-5 and -13. Dramatic increases in the expression of IL-5 and -13 and Eotaxin 2 were detected in LPS-treated BMMCs after costimulation with LPS and IgE/Ag. Overexpression of GATA1, but not GATA2, in MC9 mast cells resulted in increased transcriptional activity of IL-4, -5, and -13. Furthermore, the levels of transcription of Th2 cytokines in BMMCs were decreased by the introduction of small interfering RNA for GATA1. Thus, mast cells appear to control allergic airway inflammation after their activation and modulation through TLR4-mediated induction of GATA1 and subsequent increase in Th2 cytokine production.
Yukiko I Nigo; Masakatsu Yamashita; Kiyoshi Hirahara; Ryo Shinnakasu; Masamichi Inami; Motoko Kimura; Akihiro Hasegawa; Yoichi Kohno; Toshinori Nakayama
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Publication Detail:
Type:  Journal Article     Date:  2006-02-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-15     Completed Date:  2006-04-07     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2286-91     Citation Subset:  IM    
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
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MeSH Terms
Adoptive Transfer
Asthma / immunology*
Bone Marrow Cells / drug effects,  immunology
Cytokines / biosynthesis,  genetics
Disease Models, Animal
GATA1 Transcription Factor / metabolism
GATA2 Transcription Factor / metabolism
Lipopolysaccharides / immunology*,  pharmacology
Mast Cells / drug effects,  immunology*,  metabolism
Mice, Knockout
NF-kappa B / metabolism
Pulmonary Eosinophilia / immunology*
Respiratory Hypersensitivity / immunology*
Th2 Cells / immunology,  metabolism
Toll-Like Receptor 4 / genetics,  metabolism*
Transcription, Genetic
Reg. No./Substance:
0/Cytokines; 0/GATA1 Transcription Factor; 0/GATA2 Transcription Factor; 0/Gata1 protein, mouse; 0/Gata2 protein, mouse; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Toll-Like Receptor 4

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