Article

Role of mammalian chitinases in asthma.

Cell Division and Cancer Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, National University of Singapore, Singapore 117456, Singapore.
International Archives of Allergy and Immunology (Impact Factor: 2.43). 04/2009; 149(4):369-77. DOI: 10.1159/000205583
Source: PubMed

ABSTRACT Asthma is a chronic inflammatory disease characterized by airway inflammation, mucus hypersecretion and airway hyperresponsiveness. Mechanisms underlying the pathogenesis of asthma are not fully understood. In recent years, there are mounting evidences demonstrating that mammalian chitinases may play a key role in mediating the T-helper 2 cell-driven inflammatory response that is commonly associated with asthma. Chitinases (e.g., chitotriosidase and acidic mammalian chitinase) are enzymes that degrade chitin, the second most abundant biopolymer that can be found in the cell walls of fungi, microfilarial sheaths of helminths, and exoskeletons of insects and crustaceans. There are also chitinase-like proteins (e.g., YKL-40, Ym1 and Ym2) that lack chitinolytic activity but retain chitin-binding ability. Therefore, chitinases were originally believed to function in host defense against parasitic infections, but the first discovery of their role in inflammatory airway diseases came as a surprise. There is ample evidence to support an association of acidic mammalian chitinase and YKL-40 with allergic bronchial asthma in patients. Our recent studies in a mouse asthma model revealed that anti-inflammatory drugs like corticosteroid and cysteinyl leukotriene receptor antagonist were able to suppress elevated pulmonary levels of mammalian chitinases. Taken together, mammalian chitinases may be useful as biomarkers for asthma. Notwithstanding, large-scale multi-center association studies are required to confirm this hypothesis. Besides, substantially more works using knockout mice, recombinant chitinases and siRNA technology are required to investigate a potential role of chitinases in the pathogenesis of asthma.

0 Followers
 · 
116 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL).
    BMC Pulmonary Medicine 07/2014; 14(1):110. DOI:10.1186/1471-2466-14-110 · 2.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite several common phenotypic features, chronic obstructive pulmonary disease (COPD) and severe asthma differ with regard to their causative factors and pathophysiology. Both diseases may be exacerbated by environmental factors, however, the molecular profiles of disease episodes have not been comprehensively studied. We identified differences in gene and protein expression profiles expressed by peripheral blood mononuclear cells (PBMC) of COPD patients, patients with atopic asthma and healthy subjects when challenged with exacerbating factors in vitro: lipopolysaccharide (LPS), house dust mite (HDM) and cat allergen. PBMC isolated from patients with severe atopic asthma and COPD, as well as healthy subjects were stimulated with rDer p 1 DG, rFel d 1 DG and LPS. The changes in the expression of 47 genes belonging to five groups (phospholipase A2, eicosanoids, transcription factors, cytokines and airway remodeling) were studied using TaqMan low density array cards. Immunoblotting was used to study relative protein expression. rDer p 1 significantly up-regulated the expression of PLA2G4A, PLA2G6, PLA2G15, CYSLTR1, LB4R2, PTGS1, PTGS2, FOXP1, GATA3, HDAC2, IREB2, PPARG, STAT4, TSLP and CHI3L1 genes in asthmatics in comparison to healthy subjects. LPS induced significant expression of ANXA1 and LTA4H in asthmatics when compared to COPD patients and healthy subjects. SOX6,STAT4 and IL1RL1 were induced in COPD after LPS stimulation. Analysis of protein expression revealed a pattern similar to mRNA expression. LPS-induced exacerbation of asthma and COPD is characterized by differential expression of selected genes in PBMC. HDM allergen changed the expression profile of inflammatory genes between patients with asthma of atopic origin and healthy controls. © 2015 S. Karger AG, Basel.
    International Archives of Allergy and Immunology 01/2014; 165(4):229-43. DOI:10.1159/000370067 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As a member of 18 glycosyl hydrolase (GH) family, chitotriosidase (Chitinase 1, CHIT1) is a true chitinase mainly expressed in the differentiated and polarized macrophages. CHIT1 is an innate immune mediator that digests the cell walls of chitin-containing eukaryotic pathogens, such as fungi. However, CHIT1 is dysregulated in granulomatous and fibrotic interstitial lung diseases characterized by inflammation and tissue remodeling. These include tuberclosis, sarcoidosis, idiopathic pulmonary fibrosis, scleroderma-associated interstitial lung diseases (SSc-ILD), and chronic obstructive lung diseases (COPD). CHIT1 serum concentration correlates with the progression or the severity of these diseases, suggesting a potential use of CHIT1 as a biomarker or a therapeutic target. Recent studies with genetically modified mice demonstrate that CHIT1 enhances TGF-β1 receptor expression and signaling, suggesting a role in initiating or amplifying the response to organ injury and repair. This additional CHIT1 activity is independent of its enzymatic activity. These studies suggest that CHIT1 serves a bridging function; it is both an innate immune mediator and a regulator of tissue remodeling. This review will focus on recent data linking CHIT1 to the pathogenesis of inflammation, interstitial lung disease, and COPD.
    Allergy, asthma & immunology research 01/2015; 7(1):14-21. DOI:10.4168/aair.2015.7.1.14 · 3.08 Impact Factor