title: MUC18 Differentially Regulates Pro-Inflammatory and Anti-Viral Responses in Human Airway Epithelial Cells.
abstract: OBJECTIVE
  MUC18 or CD146, a transmembrane glycoprotein, is mainly expressed by endothelial cells and smooth muscle cells where it serves as a cell-cell adhesion molecule. We have found MUC18 up-regulation in airway epithelial cells of patients with asthma and chronic obstructive pulmonary disease (COPD). However, the function of MUC18 in airway epithelial cells remains unclear. In the present study, we tested the hypothesis that MUC18 exerts a pro-inflammatory function during stimulation with a viral mimic polyI:C or human rhinovirus infection.
  
  
  METHODS
  Normal human primary airway epithelial cells were transduced with lentivirus encoding MUC18 cDNA to over-express MUC18 or with GFP (control), and treated with polyI:C or HRV for detection of pro-inflammatory cytokine IL-8 and anti-viral gene IFN-β. Additionally, we performed cell culture of human lung epithelial cell line NCIH292 cells to determine the mechanisms of MUC18 function.
  
  
  RESULTS
  We found that MUC18 over-expression promoted IL-8 production, while it inhibited IFN-β expression following polyI:C stimulation or HRV infection. Increased phosphorylation of MUC18 serines was observed in MUC18 over-expressing cells. Reduction of MUC18 serine phosphorylation by inhibiting ERK activity was associated with less production of IL-8 following polyI:C stimulation.
  
  
  CONCLUSIONS
  Our results for the first time demonstrate MUC18's pro-inflammatory and anti-viral function in human airway epithelial cells.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Reena
authors.initials: R
authors.lastname: Berman
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Chunjian
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Finigan
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
keywords: Airway epithelial cells; Anti-viral; IL-8; Immune response; Inflammation; Interferon; MUC18; Rhinovirus