Role of Mamalian 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: 2.67). 04/2009; 149(4):369-77. DOI: 10.1159/000205583
Source: PubMed


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.

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    • "Moreover, RN was found to correlate with chitinase 3, a common biomarker in asthma. Chitinase 3 did not differentiate the two models of inflammation, although it has been suggested to play a key role in Th2 driven inflammatory response [21]. Similarly, further Th2 associated proteins, IL-5 and IL-13, correlated positively with RN. "
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    • "Plants produce chitinases to defend themselves from phytopathogenic fungi [5] [6]. In addition to other unknown functions, the mammalian chitinases have been shown to be important biomarkers in asthma [7]. "
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    Full-text · Article · Dec 2013 · International Journal of Biochemistry and Molecular Biology
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    • "Chitinase 3-like 3 (Ym1) is a member of the mammalian chitinase family that also includes Ym2 and BRP-39 in mice, and YKL-40 in humans [34]. Increased expression of these proteins has been associated with inflammatory diseases, in particular with allergic asthma, with the induction of alternative activation of macrophages, and with progression of cancer [35–39]. "
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