MUC18 Differentially Regulates Pro-Inflammatory and Anti-Viral Responses in Human Airway Epithelial Cells
|Reena Berman, Chunjian Huang, Di Jiang, James H. Finigan, Qun Wu and Hong Wei Chu*|
|Department of Medicine, National Jewish Health, Denver, CO, USA|
|Corresponding Author :||Hong Wei Chu, MD
Department of Medicine
National Jewish Health
1400 Jackson St., Room A639
Denver, CO 80206, USA
E-mail: [email protected]
|Received August 12, 2014; Accepted September 23, 2014; Published September 30, 2014|
|Citation: Berman R, Huang C, Jiang D, Finigan JH, Wu Q,et al. (2014) MUC18 Differentially Regulates Pro-Inflammatory and Anti-Viral Responses in Human Airway Epithelial Cells. J Clin Cell Immunol 5:257. doi: 10.4172/2155-9899.1000257|
|Copyright: © 2014 Berman R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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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 NCI-H292 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.