title: Gene profile of fibroblasts identify relation of CCL8 with idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is characterized by the complex interaction of cells involved in chronic inflammation and fibrosis. Global gene expression of a homogenous cell population will identify novel candidate genes.
  
  
  
  Gene expression of fibroblasts derived from lung tissues (8 IPF and 4 controls) was profiled, and ontology and functional pathway were analyzed in the genes exhibiting >2 absolute fold changes with p-values < 0.05. CCL8 mRNA and protein levels were quantified using real-time PCR and ELISA. CCL8 localization was evaluated by immunofluorescence staining.
  
  
  
  One hundred seventy eight genes differentially expressed and 15 genes exhibited >10-fold change. Among them, 13 were novel in relation with IPF. CCL8 expression was 22.8-fold higher in IPF fibroblasts. The levels of CCL8 mRNA and protein were 3 and 9-fold higher in 14 IPF fibroblasts than those in 10 control fibroblasts by real-time PCR and ELISA (p = 0.022 and p = 0.026, respectively). The CCL8 concentrations in BAL fluid was significantly higher in 86 patients with IPF than those in 41 controls, and other interstitial lung diseases including non-specific interstitial pneumonia (n = 22), hypersensitivity pneumonitis (n = 20) and sarcoidosis (n = 19) (p < 0.005, respectively). Cut-off values of 2.29 pg/mL and 0.43 pg/mL possessed 80.2 and 70.7% accuracy for the discrimination of IPF from NC and the other lung diseases, respectively. IPF subjects with CCL8 levels >28.61 pg/mL showed shorter survival compared to those with lower levels (p = 0.012). CCL8 was expressed by α-SMA-positive cells in the interstitium of IPF.
  
  
  
  Transcriptome analysis identified several novel IPF-related genes. Among them, CCL8 is a candidate molecule for the differential diagnosis and prediction of survival.
authors.affiliation: Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Korea.
authors.forename: Jong-Uk
authors.initials: JU
authors.lastname: Lee
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Sogang University, Seoul, Korea.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Shim
authors.affiliation: Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Korea.
authors.forename: Da-Jeong
authors.initials: DJ
authors.lastname: Bae
authors.affiliation: Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Korea.|Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang, University Bucheon Hospital, Bucheon, Korea.
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.affiliation: Division of Respiratory and Allergy Medicine, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 1174, Jung Dong, Wonmi-Gu, Bucheon, Gyeonggi Do, 420-021, Korea.
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University, Chunan Hospital, Cheonan, Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang, University Bucheon Hospital, Bucheon, Korea.
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Biostatistic Consulting, Soon Chun Hyang Medical Center, Bucheon, Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Sogang University, Seoul, Korea.|Department of Life Science, Sogang University, Seoul, Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Korea. mdcspark@daum.net.|Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang, University Bucheon Hospital, Bucheon, Korea. mdcspark@daum.net.
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D054412:Chemokine CCL8 / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C515453:CCL8 protein, human; D054412:Chemokine CCL8
keywords: CCL8; Gene expression; IPF; Transcriptome