ABSTRACT
Mucus hyperproduction and hypersecretion are observed often in respiratory diseases. MUC8 is a glycoprotein synthesized by epithelial cells and generally expressed in the respiratory track. However, the physiological mechanism by which extracellular nucleotides induce MUC8 gene expression in human airway epithelial cells is unclear. Here, we show that UTP could induce MUC8 gene expression through P2Y2-PLCß3-Ca2+ activation. Because the full-length cDNA sequence of MUC8 has not been identified, a specific siRNA-MUC8 was designed based on the partial cDNA sequence of MUC8. siRNA-MUC8 significantly increased TNF-α production and decreased IL-1Ra production, suggesting that MUC8 may downregulate UTP/P2Y2-induced airway inflammation. Interestingly, the PDZ peptide of ZO-1 protein strongly abolished UTP-induced TNF-α production and increased IL-1Ra production and MUC8 gene expression. In addition, the PDZ peptide dramatically increased the levels of UTP-induced ZO proteins and TEER (trans-epithelial electrical resistance). These results show that the anti-inflammatory mucin MUC8 may contribute to homeostasis, and the PDZ peptide can be a novel therapeutic candidate for UTP-induced airway inflammation.
Subject(s)
Interleukin 1 Receptor Antagonist Protein , Mucins , Humans , Mucins/genetics , Mucins/metabolism , Uridine Triphosphate/metabolism , DNA, Complementary , Tumor Necrosis Factor-alpha/metabolism , Epithelial Cells/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/metabolism , RNA, Small Interfering/metabolism , Inflammation/metabolismABSTRACT
Decoctions obtained from the dried flowers of Lonicera japonica Thunb. (Indongcho) have been utilized in folk remedies against inflammatory diseases. Recently, many agents that have used for inflammatory diseases are showing anticancer effects. Here, we have isolated polyphenols extracted from lyophilized Lonicera japonica Thunb (PELJ) and investigated the anticancer effects of PELJ on U937 cells. Here, we demonstrated that PELJ induced apoptosis by upregulation of DR4 and Fas, and further it is augmented by suppression of XIAP. In addition, The PELJ-induced apoptosis is at least in part by blocking PI3K/Akt pathway. These findings suggest that PELJ may provide evidence of anticancer activities on U937 cells. Further study for detailed mechanism and the effects on animal models is warranted to determine whether PELJ provide more conclusive evidence that PELJ which may provide a beneficial effect for treating cancer.