Allergy Asthma Immunol Res.  2010 Jan;2(1):20-27. 10.4168/aair.2010.2.1.20.

Role of breast regression protein-39/YKL-40 in asthma and allergic responses

• Lee CG
• Elias JA

• KMID: 2260415
• DOI: http://doi.org/10.4168/aair.2010.2.1.20

Abstract

BRP-39 and its human homolog YKL-40 have been regarded as a prototype of chitinase-like proteins (CLP) in mammals. Exaggerated levels of YKL-40 protein and/or mRNA have been noted in a number of diseases characterized by inflammation, tissue remodeling, and aberrant cell growth. Asthma is an inflammatory disease characterized by airway hyperresponsiveness and airway remodeling. Recently, the novel regulatory role of BRP-39/YKL-40 in the pathogenesis of asthma has been demonstrated both in human studies and allergic animal models. The levels of YKL-40 are increased in the circulation and lungs from asthmatics where they correlate with disease severity, and CHI3L1 polymorphisms correlate with serum YKL-40 levels, asthma and abnormal lung function. Animal studies using BRP-39 null mutant mice demonstrated that BRP-39 was required for optimal allergen sensitization and Th2 inflammation. These studies suggest the potential use of BRP-39 as a biomarker as well as a therapeutic target for asthma and other allergic diseases. Here, we present an overview of chitin/chitinase biology and summarize recent findings on the role of BRP-39 in the pathogenesis of asthma and allergic responses.

Keyword

BRP-39; human CHI3L1 protein; asthma; hypersensitivity

MeSH Terms

Airway Remodeling
Animals
Asthma
Biology
Breast
Humans
Hypersensitivity
Inflammation
Lung
Mammals
Mice
Models, Animal
Proteins
RNA, Messenger
Proteins
RNA, Messenger

Figure

• 

  Fig. 1 The proposed regulatory pathway of BRP-39 in allergic inflammation and tissue remodeling. Macrophages and epithelial cells are the primary cells expressing BRP-39 in the lung after allergen sensitization and challenge. BRP-39 increases the dendritic cell numbers in the lung and further activates and leads to enhanced Th2 polarization. BRP-39 also increases Th2 cells by reduction of T cell apoptosis or increase of cell survival. TGF-β or other growth factors produced by Th2 cytokine stimulation leads to airway or alveolar remodeling. BRP-39 and Th2 cytokines such as IL-13 or IL-4 further contribute to the production of BRP-39 via regulation of cell death responses or alternative macrophage activation.

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