title: Protective effects of elafin against adult asthma.
abstract: BACKGROUND
  Elafin inhibits serine proteases, such as human neutrophil elastase and proteinase 3, to prevent excessive damage during inflammation. However, the relationship between elafin and asthma is still unclear. Microarray technology was used to evaluate smoking- and asthma-related biomarkers in a discovery-driven manner. We identified candidate genes, e.g., proteinase inhibitor 3 (PI3), related to asthma and smoking from gene expression microarray data sets and evaluated their potential as biomarkers for asthma.
  
  
  METHODS
  We used human genome microarray data sets from smoking- and asthma-related gene expression data sets and performed real-time quantitative polymerase chain reaction to measure and validate differences in gene expression. We also recruited adult patients with asthma and age- and sex-matched control patients who were administered a structured questionnaire and evaluated for lung function and plasma elafin levels, which are encoded by the PI3 gene.
  
  
  RESULTS
  Six significantly altered candidate genes, PI3, protein kinase C iota, phosphoserine phosphatase, IQ motif-containing GTPase activating protein 1, interleukin 13 receptor α 1, and signal transducing adaptor molecule SH3 domain and ITAM motif 2, were identified from comparisons across the four asthma- and four smoking-related data sets included in this study. An in vitro study of human airway epithelial cells (A549) and a human monocytic cell line (THP-1) demonstrated that PI3 messenger RNA levels were significantly altered by nicotine exposure. Elafin concentration was significantly higher in control patients than in patients with asthma (p < 0.001). The plasma elafin concentration in the highest quartile (≥12.69 ng/mL) was inversely associated with asthma (adjusted odds ratio 0.122 [95% confidence interval, 0.053-0.278]) compared with the lowest quartile (<5.82 ng/mL) after adjusting for age, sex, smoking status, waist-to-hip ratio, percentage predicted forced expiratory volume in 1 second, cockroaches in the home, incense burning, and family history.
  
  
  CONCLUSIONS
  Our study revealed that high elafin levels identified in smoking- and asthma-related microarray data sets and an epidemiologic study significantly reduced the risk of asthma. Further studies of elafin as a potential therapy for asthma are warranted.
authors.affiliation: Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Tsai
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tseng
authors.forename: Pei-Shih
authors.initials: PS
authors.lastname: Chen
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Wu
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Chin-Chou
authors.initials: CC
authors.lastname: Wang
authors.forename: Kang-Shin
authors.initials: KS
authors.lastname: Chen
authors.forename: Yuan-Chung
authors.initials: YC
authors.lastname: Lin
authors.forename: Tsu-Nai
authors.initials: TN
authors.lastname: Wang
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D053492:Elafin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011480:Protease Inhibitors / Q000097:blood / Q000378:metabolism*; D012129:Respiratory Function Tests; D012307:Risk Factors; D012907:Smoking
chemical_list: D015415:Biomarkers; D053492:Elafin; D011480:Protease Inhibitors; D007073:Immunoglobulin E