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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
 Chun Geun Lee  ;  Dominik Hartl  ;  Gap Ryol Lee  ;  Barbara Koller  ;  Hiroshi Matsuura  ;  Carla A. Da Silva  ;  Myung Hyun Sohn  ;  Lauren Cohn  ;  Robert J. Homer  ;  Alexander A. Kozhich  ;  Alison Humbles  ;  Jennifer Kearley  ;  Anthony Coyle  ;  Geoffrey Chupp  ;  Jennifer Reed  ;  Richard A. Flavell  ;  Jack A. Elias 
Citation
 JOURNAL OF EXPERIMENTAL MEDICINE, Vol.206(5) : 1149-1166, 2009 
Journal Title
 JOURNAL OF EXPERIMENTAL MEDICINE 
ISSN
 0022-1007 
Issue Date
2009
MeSH
Adipokines ; Animals ; Apoptosis/genetics ; Apoptosis/physiology* ; Asthma/genetics ; Chitinase-3-Like Protein 1 ; Conserved Sequence ; Coronary Disease/genetics ; Glycoproteins/deficiency ; Glycoproteins/genetics* ; Glycoproteins/therapeutic use ; Humans ; Immunoglobulin E/immunology ; Inflammation/chemically induced ; Inflammation/genetics* ; Inflammation/pathology ; Interleukin-13/genetics* ; Lectins ; Mice ; Mice, Knockout ; Mice, Transgenic ; Ovalbumin
Abstract
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
Files in This Item:
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DOI
10.1084/jem.20081271
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104912
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