20656949

pubmed:Citation

6

The exaggerated expression of chitinase-like protein YKL-40, the human homologue of breast regression protein-39 (BRP-39), was reported in a number of diseases, including chronic obstructive pulmonary disease (COPD). However, the in vivo roles of YKL-40 in normal physiology or in the pathogenesis of specific diseases such as COPD remain poorly understood. We hypothesized that BRP-39/YKL-40 plays an important role in the pathogenesis of cigarette smoke (CS)-induced emphysema. To test this hypothesis, 10-week-old wild-type and BRP-39 null mutant mice (BRP-39(-/-)) were exposed to room air (RA) and CS for up to 10 months. The expression of BRP-39 was significantly induced in macrophages, airway epithelial cells, and alveolar Type II cells in the lungs of CS-exposed mice compared with RA-exposed mice, at least in part via an IL-18 signaling-dependent pathway. The null mutation of BRP-39 significantly reduced CS-induced bronchoalveolar lavage and tissue inflammation. However, CS-induced epithelial cell apoptosis and alveolar destruction were further enhanced in the absence of BRP-39. Consistent with these findings in mice, the tissue expression of YKL-40 was significantly increased in the lungs of current smokers compared with the lungs of ex-smokers or nonsmokers. In addition, serum concentrations of YKL-40 were significantly higher in smokers with COPD than in nonsmokers or smokers without COPD. These studies demonstrate a novel regulatory role of BRP-39/YKL-40 in CS-induced inflammation and emphysematous destruction. These studies also underscore that maintaining physiologic concentrations of YKL-40 in the lung is therapeutically important in preventing excessive inflammatory responses or emphysematous alveolar destruction.

eng

IM

MEDLINE

1535-4989

Electronic

NLM

777-86

pubmed-meshheading:20656949-Adipokines, pubmed-meshheading:20656949-Aged, pubmed-meshheading:20656949-Animals, pubmed-meshheading:20656949-Emphysema, pubmed-meshheading:20656949-Female, pubmed-meshheading:20656949-Glycoproteins, pubmed-meshheading:20656949-Humans, pubmed-meshheading:20656949-Inflammation, pubmed-meshheading:20656949-Interleukin-18, pubmed-meshheading:20656949-Lectins, pubmed-meshheading:20656949-Lung, pubmed-meshheading:20656949-Male, pubmed-meshheading:20656949-Mice, pubmed-meshheading:20656949-Mice, Inbred C57BL, pubmed-meshheading:20656949-Mice, Transgenic, pubmed-meshheading:20656949-Middle Aged, pubmed-meshheading:20656949-Pulmonary Disease, Chronic Obstructive, pubmed-meshheading:20656949-Signal Transduction, pubmed-meshheading:20656949-Smoke, pubmed-meshheading:20656949-Smoking

Role of breast regression protein-39 in the pathogenesis of cigarette smoke-induced inflammation and emphysema.

Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural