title: IL-27 is elevated in patients with COPD and patients with pulmonary TB and induces human bronchial epithelial cells to produce CXCL10.
abstract: BACKGROUND
  The role of IL-27 in the pathogenesis of airway inflammatory diseases remains elusive. We, therefore, have studied its concentrations in the sputum and plasma of patients with COPD and patients with pulmonary TB (PTB), and further investigated the mechanism-of-action effects of IL-27 on bronchial epithelial cells in vitro.
  
  
  METHODS
  Human bronchial epithelial cells grown on air-liquid interface culture were activated by IL-27, alone, or in combination with other inflammatory cytokines in the presence or absence of various signaling molecule inhibitors. The expression of CXCL10 was detected by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). The underlying signaling pathways were studied by intracellular staining using flow cytometry, Western blot, ELISA, or siRNA.
  
  
  RESULTS
  Significantly higher sputum and plasma concentrations of IL-27 were found in patients with COPD (n = 34; P < .01 and P < .001, respectively) or patients with PTB (n = 31; P < .01 and P < .001, respectively) than in healthy control subjects (n = 48). Sputum, but not plasma, IL-27 levels in patients with COPD correlated negatively with FEV(1) (r = -0.51, P < .01). Sputum, but not plasma, IL-27 in patients with PTB correlated positively with mycobacterial load in sputum (r = 0.48, P < .05). Further in vitro studies demonstrated that IL-27 could induce gene and protein expression of CXCL10 in bronchial epithelial cells, which was regulated by the activation of the phosphatidylinositol 3-OH kinase (PI3K)-Akt signaling pathway.
  
  
  CONCLUSIONS
  The production of IL-27 is related to the pathogenesis of COPD and PTB, and IL-27 induces the expression of CXCL10 in bronchial epithelial cells through the activation of the PI3K-Akt signaling pathway.
authors.affiliation: Department of Laboratory Medicine, Chongqing, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Laboratory Medicine, Chongqing, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Disease, Chongqing, China.
authors.forename: Dairong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Emergency and Intensive Care Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Chongqing, China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, Chongqing, China. Electronic address: renguosheng726@163.com.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013183:Sputum / Q000737:chemistry / Q000166:cytology; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007378:Interleukins; C464565:MYDGF protein, human; D004247:DNA