Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Proc Natl Acad Sci U S A ; 103(7): 2286-91, 2006 Feb 14.
Article in English | 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.


Subject(s)
Asthma/immunology , Lipopolysaccharides/immunology , Mast Cells/immunology , Pulmonary Eosinophilia/immunology , Respiratory Hypersensitivity/immunology , Toll-Like Receptor 4/metabolism , Adoptive Transfer , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/immunology , Cytokines/biosynthesis , Cytokines/genetics , Disease Models, Animal , GATA1 Transcription Factor/metabolism , GATA2 Transcription Factor/metabolism , Lipopolysaccharides/pharmacology , Mast Cells/drug effects , Mast Cells/metabolism , Mice , Mice, Knockout , NF-kappa B/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Toll-Like Receptor 4/genetics , Transcription, Genetic
2.
J Biol Chem ; 279(38): 39454-64, 2004 Sep 17.
Article in English | MEDLINE | ID: mdl-15258154

ABSTRACT

Interleukin (IL)-4-induced STAT6 activation and the subsequent up-regulation of GATA3 are crucial for the induction of chromatin remodeling of the Th2 cytokine gene loci as Th2 cells undergo development. This study probes the role of these molecules in the maintenance of memory Th2 cells. IL-4 was not required to maintain the capability for Th2 cytokine production in in vivo generated antigen-specific memory Th2 cells. Histone H3-K9/14 hyperacetylation and intergenic transcripts associated with the IL-4 gene locus were preserved in the absence of IL-4, but those associated with the IL-13 gene were partially IL-4-dependent. Histone H3-K4 methylation of the IL-13 and IL-4 gene loci was fully preserved in memory Th2 cells and accompanied by memory cell-specific accumulation of Pol II complex to highly restricted sites. Thus, memory Th2 cells maintain a unique Th2-specific remodeled chromatin in the IL-4 and IL-13 gene loci by active molecular events that are IL-4-independent.


Subject(s)
Histones/metabolism , Immunologic Memory/physiology , Interleukin-4/genetics , Th2 Cells/physiology , Acetylation , Adoptive Transfer , Animals , Cytokines/metabolism , DNA Polymerase II/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Enhancer Elements, Genetic/physiology , Epitopes/genetics , GATA3 Transcription Factor , Interleukin-13/genetics , Methylation , Mice , Mice, Inbred BALB C , Mice, Nude , Mice, Transgenic , Promoter Regions, Genetic/physiology , RNA, Messenger/analysis , Trans-Activators/genetics , Trans-Activators/metabolism
3.
J Infect Chemother ; 10(1): 31-6, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14991515

ABSTRACT

To date, the technique of washed sputum examinations has not been widely used in the clinical management of lower respiratory tract infections in children. A total of 224 sputum samples from 125 pediatric patients with lower respiratory tract infections were collected for washed sputum Gram stain smears and cultures. The results with these methods were compared to find correlation rates. The value of washed sputum cultures was assessed by examining the clinical responses of the patients who received antibiotic therapies instituted on the basis of the sputum culture results. Isolation rates of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus were 22.4%, 9.4%, 4.9%, and 0.4%, respectively. For the prediction of H. influenzae, S. pneumoniae, and M. catarrhalis, the sensitivities of the washed sputum Gram stain smears compared with the culture method were 86.0%, 81.0%, and 90.9%, respectively. The specificities of the washed sputum Gram stain smear technique were 94.8%, 97.5%, and 98.1%, respectively. Overall, the sensitivity and specificity of the washed sputum Gram stain smear method were 85.5% and 87.2%, respectively. S. aureus was isolated from only one specimen; and washed sputum Gram stain smear estimation was correlated with the culture result. On the basis of the washed sputum culture results, appropriate antibiotic therapies were instituted for 93.3% of the patients with acute lower respiratory tract infections. This study suggests that the techniques of washed sputum Gram stain smear and culture are valuable and should be encouraged in clinical practice for the management of lower respiratory tract infections in children.


Subject(s)
Bacteriological Techniques , Pneumonia, Bacterial/diagnosis , Sputum/microbiology , Staining and Labeling , Child , Child, Preschool , Female , Haemophilus influenzae/isolation & purification , Humans , Infant , Japan/epidemiology , Male , Moraxella catarrhalis/isolation & purification , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/microbiology , Predictive Value of Tests , Sensitivity and Specificity , Staphylococcus aureus/isolation & purification , Streptococcus pneumoniae/isolation & purification
4.
Immunity ; 19(2): 281-94, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12932361

ABSTRACT

Chromatin remodeling of type 2 cytokine gene loci occurs during differentiation of naive CD4 and CD8 T cells into type 2 helper (Th2) and cytotoxic (Tc2) T cells. IL-4 production and histone hyperacetylation in IL-4-associated nucleosomes in developing Tc2 cells were significantly lower than those of Th2 cells; however, cytokine production and histone hyperacetylation of IL-5 and IL-13 genes were equivalent. Developing Tc2 cells expressed lower GATA3 levels and dramatically increased levels of repressor of GATA (ROG). A ROG response element in the IL-13 gene exon 4 displayed Tc2-specific binding of ROG, HDAC1, and HDAC2 and exhibited repression of IL-4 gene activation. Thus, ROG may confer CD8 T cell-specific repression of histone hyperacetylation and activation of the IL-4 gene locus.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Histones/metabolism , Interleukin-4/genetics , Repressor Proteins/metabolism , Acetylation , Animals , Base Sequence , CD8-Positive T-Lymphocytes/cytology , Calcineurin/genetics , Calcineurin/metabolism , Cell Differentiation , Cell Division , DNA/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Down-Regulation , GATA3 Transcription Factor , Gene Expression Regulation , Histones/chemistry , Interleukin-13/genetics , Interleukin-4/biosynthesis , MAP Kinase Signaling System , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Proto-Oncogene Proteins c-raf/genetics , Proto-Oncogene Proteins c-raf/metabolism , Trans-Activators/genetics , Trans-Activators/metabolism , Transcriptional Activation
SELECTION OF CITATIONS
SEARCH DETAIL
...