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Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis.

Authors: 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 
Citation: Lee CG, etal., J Exp Med. 2009 May 11;206(5):1149-66. Epub 2009 May 4.
Pubmed: (View Article at PubMed) PMID:19414556
DOI: Full-text: DOI:10.1084/jem.20081271

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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CRRD Object Information
CRRD ID: 4892663
Created: 2011-02-28
Species: All species
Last Modified: 2011-02-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.