Leptin positively regulates MUC5AC production and secretion induced by interleukin-13 in human bronchial epithelial cells.

Leptin positively regulates MUC5AC production and secretion induced by interleukin-13 in human bronchial epithelial cells. Biochem Biophys Res Commun. 2017 Nov 18;493(2):979-984 Authors: Hao W, Wang J, Zhang Y, Wang Y, Sun L, Han W Abstract Mucus hypersecretion and plugging of lower respiratory tract airways due to mucus plugs have long been recognized as the leading cause of the morbidity and mortality in asthma. MUC5AC protein is a major component of airway mucus. Here, we showed that interleukin (IL)-13 induced MUC5AC production and secretion, and leptin expression in the human bronchial epithelial cell line-16 (HBE16) cells in a concentration-dependent manner. Leptin knockdown suppressed MUC5AC production and secretion induced by IL-13. We further investigated the molecular mechanism by which leptin functioned, and found that leptin regulated IL-13-induced MUC5AC production and secretion via the JAK2-STAT3 pathway. Subsequently, Munc18b, a limiting component of the exocytic machinery of airway epithelial and mast cells, was found that when knockdown, MUC5AC secretion was significantly inhibited. SABiosciences ChIP search tool identified three STAT3 binding sites with Munc18b promoter. Chromatin immunoprecipitation analysis further confirmed that Stat3 upregulated Munc18b expression by directly binding to its promoter. These data suggested that leptin promotes MUC5AC secretion via JAK2-STAT3-MUNC18b regulatory network. Taken toget...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research