Role of Mammalian Chitinases in Asthma

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.

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

“…Increased expression of these proteins has been associated with inflammatory diseases, in particular with allergic asthma (reviewed in (Lee et al, 2008;Shuhui et al, 2009). The physiological function of Ym1 is not clear, but a role in eosinophil chemotaxis (Owhashi et al, 2000) and promotion of cytokine production (Cai et al, 2009) has been suggested.…”

Distribution of Chitinolytic Enzymes in the Organs and cDNA Cloning of Chitinase Isozymes from the Stomach of Two Species of Fish, Chub Mackerel (<i>Scomber japonicus</i>) and Silver Croaker (<i>Pennahia argentata</i>)

“…Although the majority of studies on chitinase have been conducted on microorganisms [12], chitinase is also found and has been investigated in many other biological species, including mammals [13]- [15], fish [16]- [19], mollusks [20] [21], insects [22]- [24], plants [22] [25], and fungi [1] [22]. Since the physiological role of chitinase varies in these organisms, the mechanism and efficiency of chitinase degradation and the substrate specificity have been reported to vary.…”

“…For instance, acidic mammalian chitinase expressed in the stomach of mammals [26], and chitotriosidase produced by macrophages [14] [15] are thought to function in the digestion and absorption of food and defense against pathogens. In addition, chitinase has been detected at the onset of asthma and allergies, suggesting its involvement in diseases [13] [15]. In contrast, chitinase and Hex are also found in the digestive tracts of fish.…”

YKL-40 Induces IL-8 Expression from Bronchial Epithelium via MAPK (JNK and ERK) and NF-κB Pathways, Causing Bronchial Smooth Muscle Proliferation and Migration

“…Since it was identified in 1993 as a secreted product of articular chondrocytes and synovial cells (9), a growing body of evidence has shown that high serum levels of YKL-40 are associated with various pathological conditions such as allergic diseases (10)(11)(12). In terms of lung diseases, high serum levels of YKL-40 are associated with asthma (13,14), chronic obstructive pulmonary disease (15), and lung cancer (16).…”