{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Matsuura H"],"funding":["NHLBI NIH HHS"],"pagination":["777-86"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3135840"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(6)"],"pubmed_abstract":["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."],"journal":["American journal of respiratory cell and molecular biology"],"pubmed_title":["Role of breast regression protein-39 in the pathogenesis of cigarette smoke-induced inflammation and emphysema."],"pmcid":["PMC3135840"],"funding_grant_id":["HL-093027","HL-084225","HL-081639","K08 HL103770"],"pubmed_authors":["Lee CG","Hartl D","Kang MJ","Homer RJ","Elias JA","Koller B","Cho WK","Zhou Y","Matsuura H","Dela Cruz CS","Chupp GL"],"additional_accession":[]},"is_claimable":false,"name":"Role of breast regression protein-39 in the pathogenesis of cigarette smoke-induced inflammation and emphysema.","description":"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.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Jun","modification":"2025-04-04T23:39:47.826Z","creation":"2019-03-27T03:07:02Z"},"accession":"S-EPMC3135840","cross_references":{"pubmed":["20656949"],"doi":["10.1165/rcmb.2010-0081OC","10.1165/rcmb.2010-0081oc"]}}