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Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function.
Nigo, Yukiko I; Yamashita, Masakatsu; Hirahara, Kiyoshi; Shinnakasu, Ryo; Inami, Masamichi; Kimura, Motoko; Hasegawa, Akihiro; Kohno, Yoichi; Nakayama, Toshinori.
Afiliação
  • Nigo YI; Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
Proc Natl Acad Sci U S A ; 103(7): 2286-91, 2006 Feb 14.
Article em En | MEDLINE | ID: mdl-16461458
ABSTRACT
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Eosinofilia Pulmonar / Hipersensibilidade Respiratória / Asma / Lipopolissacarídeos / Receptor 4 Toll-Like / Mastócitos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2006 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Eosinofilia Pulmonar / Hipersensibilidade Respiratória / Asma / Lipopolissacarídeos / Receptor 4 Toll-Like / Mastócitos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2006 Tipo de documento: Article