Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis.
Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis.
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DOI：
10.1084/jem.20081271
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发表时间：
2009-05-11
期刊：
影响因子：
--
通讯作者：
Elias JA
中科院分区：
文献类型：
--
作者：
Lee CG;Hartl D;Lee GR;Koller B;Matsuura H;Da Silva CA;Sohn MH;Cohn L;Homer RJ;Kozhich AA;Humbles A;Kearley J;Coyle A;Chupp G;Reed J;Flavell RA;Elias JA
小鼠乳腺消退蛋白39 （BRP-39; Chi3l1）及其人类同源物YKL-40是几丁质酶样蛋白，缺乏几丁质酶活性。尽管YKL-40在哮喘和许多其他疾病中表达量过高且与疾病活动性相关，但BRP-39/YKL-40的生物学特性仅被初步定义。我们描述了BRP-39−/−小鼠、YKL-40转基因小鼠和缺乏BRP-39且仅在肺上皮中产生YKL-40的小鼠的产生和特性。这些小鼠的研究表明，BRP-39−/−动物明显减少抗原诱导的Th2反应，上皮细胞YKL-40恢复了这些动物的Th2反应。在缺乏BRP-39的情况下，白细胞介素13诱导组织炎症和纤维化的能力也明显减弱。机制研究表明，BRP-39和YKL-40在抗原致敏和免疫球蛋白E诱导、刺激树突状细胞积累和活化、诱导巨噬细胞选择性活化等方面发挥重要作用。这些蛋白还抑制炎症细胞凋亡/细胞死亡，同时抑制Fas表达，激活蛋白激酶B/AKT，诱导Faim 3。这些研究确立了BRP-39/YKL-40在Th2炎症和重塑的起始和效应阶段的新调控作用，并表明这些蛋白是Th2和巨噬细胞介导的疾病的治疗靶点。
Mouse breast regression protein 39 (BRP-39; Chi3l1) and its human homologue YKL-40 are chitinase-like proteins that lack chitinase activity. Although YKL-40 is expressed in exaggerated quantities and correlates with disease activity in asthma and many other disorders, the biological properties of BRP-39/YKL-40 have only been rudimentarily defined. We describe the generation and characterization of BRP-39−/− mice, YKL-40 transgenic mice, and mice that lack BRP-39 and produce YKL-40 only in their pulmonary epithelium. Studies of these mice demonstrated that BRP-39−/− animals have markedly diminished antigen-induced Th2 responses and that epithelial YKL-40 rescues the Th2 responses in these animals. The ability of interleukin13 to induce tissue inflammation and fibrosis was also markedly diminished in the absence of BRP-39. Mechanistic investigations demonstrated that BRP-39 and YKL-40 play an essential role in antigen sensitization and immunoglobulin E induction, stimulate dendritic cell accumulation and activation, and induce alternative macrophage activation. These proteins also inhibit inflammatory cell apoptosis/cell death while inhibiting Fas expression, activating protein kinase B/AKT, and inducing Faim 3. These studies establish novel regulatory roles for BRP-39/YKL-40 in the initiation and effector phases of Th2 inflammation and remodeling and suggest that these proteins are therapeutic targets in Th2- and macrophage-mediated disorders.
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影响因子：
2
作者：
Kawada, Mayumi;Hachiya, Yuriko;Mizoguchi, Emiko
通讯作者：
Mizoguchi, Emiko
影响因子：
15.9
作者：
Becart, Stephane;Charvet, Celine;Altman, Amnon
通讯作者：
Altman, Amnon
影响因子：
4.6
作者：
Johansen, J. S.;Pedersen, A. N.;Bruunsgaard, H.
通讯作者：
Bruunsgaard, H.
影响因子：
15.9
作者：
Lambrecht, BN;De Veerman, M;Pauwels, RA
通讯作者：
Pauwels, RA
DOI：
10.1084/jem.194.6.809
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Homer RJ;Zhu Z;Lanone S;Wang X;Koteliansky V;Shipley JM;Gotwals P;Noble P;Chen Q;Senior RM;Elias JA
通讯作者：
Elias JA