MUC18 regulates IL-13-mediated airway inflammatory response

Abstract

To evaluate the effects of MUC18 on IL-13-mediated airway inflammatory responses in human airway epithelial cells and in mice. Primary normal human tracheobronchial epithelial (HTBE) cells, wild-type (WT) and Muc18 knockout (KO) mice, and mouse tracheal epithelial cells (mTECs) were utilized. Cultured HTBE cells treated with MUC18 siRNA or MUC18 expressing lentivirus were incubated with IL-13 (10ng/mL) for 24h. Mice were intranasally instilled with 500ng of IL-13 for 3days. mTECs were treated with IL-13 (10ng/mL) for 3days. PCR was used to measure mRNA expression. Western Blot and ELISAs were used to quantify protein expression. Cytospins of bronchoalveolar lavage (BAL) cells were used to obtain leukocyte differentials. MUC18 siRNA reduced IL-13-mediated eotaxin-3 (183±44 vs. 380±59pg/mL, p<0.05), while MUC18 overexpression increased IL-13-mediated eotaxin-3 (95±3 vs. 58±3pg/mL, p<0.05) in HTBE cells. IL-13-treated Muc18 KO mice had a lower percentage of neutrophils in BAL than WT mice (25±3 vs. 35±3%, p=0.0565). These results implicate MUC18 as a potential enhancer of airway inflammation in a type 2 cytokine (e.g., IL-13) milieu.