Article

Progress in Allergy Signal Research on Mast Cells: Regulation of Allergic Airway Inflammation Through Toll-Like Receptor 4–Mediated Modification of Mast Cell Function

Department of Immunology, Graduate School of Medicine, Chiba University, Japan.
Journal of Pharmacological Sciences (Impact Factor: 2.36). 04/2008; 106(3):332-5. DOI: 10.1254/jphs.FM0070202
Source: PubMed

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 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.

0 Followers
 · 
6 Reads
  • Source
    • "According to previous studies, 2 common gene polymorphism sites are present in the extracellular region of TLR4, at positions -896 (A→G) and -1196 (C→T), which alter the amino acids 299 and 399, respectively, and reduce the protein's sensitivity to LPS, thereby facilitating infection with Gram-negative bacteria. Yamashita and Nakayama (2008) showed that TLR4 plays an important role in allergic reactions in the respiratory tract. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the associations between single nucleotide polymorphisms (SNPs) and haplotypes of the genes encoding a disintegrin and metalloproteinase 33 (ADAM33), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) and the susceptibility of developing specific adult phenotypes of bronchial asthma in a Chinese Uygur population. Five SNPs of ADAM33 (T1, T2, and V4), 3 SNPs of CD14 (-1359G/T, -1145G/A, and -159T/C), and 2 SNPs of TLR4 (-896A/G and -1196C/T) were genotyped in a Chinese Uygur sample of 126 adult asthmatic patients and 126 control subjects. Gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism analysis. The genotyping results were confirmed in a random subgroup of our samples using direct DNA sequencing. The allele frequencies of ADAM33 T1 (TC), T2 (AG), and V4 (GG) were significantly higher in patients than in controls (P < 0.05). The genotypes T1 (TC+CC), T2 (AG+AA), and V4 (CG+GG) significantly increased the risk of asthma. After adjusting for confounding factors, these associations were stronger and remained significant. The T1 (TC) and V4 (GG) genotypes in the ADAM33 gene were associated with significantly decreased FEV1 levels in patients with asthma. The haplotype frequencies of Hap3 (CAC) and Hap4 (CAG) were significantly higher in patients than in controls (P < 0.05). Our results suggest that polymorphisms T1, T2, and V4 in ADAM33 may contribute to the susceptibility to asthma. Specific haplotypes of ADAM33 may contribute to a higher susceptibility to asthma in the Chinese Uygur population.
    Preview · Article · Jun 2014 · Genetics and molecular research: GMR
  • [Show abstract] [Hide abstract]
    ABSTRACT: Allergic rhinitis (AR) affects about six hundred million people worldwide and is now considered the most prevalent recurrent disease. The pathogenesis of AR involves a complex network of cellular and humoral mediators involved in the Th2 immune profile. Together with the adaptive immune system, components of innate immunity have shown to play an important role in allergic diseases such as atopic dermatitis and bronchial asthma. The present review describes the role of Toll-like receptors in allergic rhinitis. We discuss the importance of the receptors expression, function and modulation in this disease.
    No preview · Article ·
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Racemic albuterol is an equimolar mixture of two isomers, (R) and (S). Whether (R) and (S) isomers and the combination of both exert different effects in immune activation is not well defined. We analyzed the effects of (R+S)-albuterol, (R)-albuterol and (S)-albuterol in a murine model of allergic pulmonary inflammation and in activated T cells. Mice (C57BL/6) sensitized and aerosol challenged with the allergen ovalbumin (OVA) or phosphate buffered saline (PBS) were treated with (R)-albuterol, (S)-albuterol or (R+S)-albuterol. Following administration of (R)-albuterol, allergen induced bronchoalveolar lavage eosinophils and IgE showed a decrease, albeit not significantly by ANOVA. As T cells are important in allergic inflammation, we asked whether (R+S), (R) or (S)-albuterol might differ in effects on T cells and on the activity of the inflammatory transcription factor NF-kappaB. In activated T cells, (R)-albuterol administration decreased levels of inflammatory cytokines and NF-kappaB activity. These studies suggest that (R)-albuterol decreases cytokine secretion and NF-kappaB activity in T cells.
    Full-text · Article · Feb 2008 · Respiratory research
Show more