Role of mammalian chitinases in inflammatory conditions
Role of mammalian chitinases in inflammatory conditions
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DOI：
10.2302/kjm.56.21
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发表时间：
2007-03-01
影响因子：
2
通讯作者：
Mizoguchi, Emiko
中科院分区：
文献类型：
--
作者：
Kawada, Mayumi;Hachiya, Yuriko;Mizoguchi, Emiko
据推测，失调的宿主/微生物相互作用在炎症性肠病的发病机制中起着关键作用。然而，肠道疾病的诱导和持续的确切机制尚不清楚。最近，我们意外地发现显着上调几丁质酶3样1基因表达的葡聚糖硫酸钠诱导的结肠炎模型的结肠炎，通过采用DNA微阵列分析。几丁质酶3-like-1具有几丁质结合能力，但缺乏裂解微生物细胞壁的酶活性。几丁质酶3样1蛋白主要表达于葡聚糖硫酸钠诱导的炎症结肠的结肠上皮细胞和巨噬细胞。几丁质酶3-like-1在促炎细胞因子刺激后可上调，具有增强细胞内细菌粘附和内化至结肠上皮细胞的能力。最重要的是，在体内中和几丁质酶3样-1显着抑制葡聚糖硫酸钠诱导的结肠炎的发展，显着减少细菌粘附和侵入结肠上皮细胞。此外，与对照兔IgG处理的小鼠相比，抗几丁质酶3样1抗体处理的小鼠在外周器官中表现出显著较低的鼠伤寒沙门氏菌负荷。最近，有报道称，酸性哺乳动物几丁质酶在T辅助细胞-2相关的炎症中表达，随后诱导过敏性哮喘患者的气道高反应性。此外，泛几丁质酶抑制剂显着改善T辅助细胞-2介导的炎症和气道过敏。这些研究为深入了解哺乳动物几丁质酶在宿主/微生物相互作用中的生理作用提供了新的视角，抑制几丁质酶活性将被认为是过敏性和炎症性疾病的一种新的治疗策略。
It has been hypothesized that dysregulated host/microbial interactions play a pivotal role in the pathogenesis of inflammatory bowel disease. However, the exact mechanisms underlying the induction and perpetuation of the intestinal disorder are unclear. Recently, we unexpectedly discovered significantly upregulated gene expression of chitinase 3-like-1 in inflamed colon of the dextran sulfate sodium-induced colitis model by employing the DNA-microarray analysis. Chitinase 3-like-1 has a chitin binding ability, but lacks the enzymatic activity of lysing microbial cell wall. Chitinase 3-like-1 protein is mainly expressed in colonic epithelial cells and macrophages in the inflamed colon of dextran sulfate sodium-induced colitis. Chitinase 3-like-1, which can be upregulated after pro-inflammatory cytokine stimulation, possesses an ability to enhance the adhesion and internalization of intracellular bacteria into colonic epithelial cells. Most importantly, in vivo neutralization of chitinase 3-like-1 significantly suppressed the development of dextran sulfate sodium-induced colitis by dramatically decreasing the bacterial adhesion and invasion into colonic epithelial cells. Furthermore, anti-chitinase 3-like-1 antibody-treated mice exhibited a significantly lower load of Salmonella typhimurium in peripheral organs as compared to control rabbit IgG-treated mice. Recently, it has been reported that acidic mammalian chitinase is expressed in the setting of T helper-2-associated inflammation and subsequently induces airway hyper-responsiveness in allergic asthma patients. In addition, pan-chitinase inhibitor significantly ameliorates T helper-2-mediated inflammation and airway hypersensitivity. These studies provide to be a novel insight into the physiological role of mammalian chitinases in host/microbial interactions, and inhibition of chitinase activity would be considered a novel therapeutic strategy of allergic and inflammatory disorders.