Abstract
Background: Non-autologous and autologous cytosolic DNA are recognized as danger signals by cytoplasmic sensor molecules that activate signal-transduction pathways. An important molecule in cytosolic DNA sensing is stimulator of interferon genes (STING), an endoplasmic reticulum protein activated by cyclic GMP–AMP (cGAMP) produced in response to cytosolic DNA. STING is important for innate immune responses to cytosolic DNA in immune cells; however, knowledge about its role in bronchial epithelial cells is limited. Methods: We stimulated NCI-H292 cells with poly(dA:dT) and silenced STING and other regulatory proteins, and then determined MUC5AC mRNA expression levels. Results: Cytosolic DNA increased the expression of a major respiratory mucin protein, MUC5AC, in the human respiratory epithelial cell line NCI-H292 in a STING-dependent manner. Introducing poly(dA:dT) into the cytoplasm induced MUC5AC and interferon-β (IFNβ) expression. Silencing STING by RNA interference decreased poly(dA:dT)-induced MUC5AC mRNA expression but increased IFN-β mRNA levels. Furthermore, cGAMP treatment increased MUC5AC expression but not IFN-β expression. In contrast, silencing retinoic acid-inducible gene-I (RIG-I), which is a component of a different nucleic acid-sensing system, suppressed poly(dA:dT)-induced IFN-β expression and increased MUC5AC expression. Conclusions: Unlike its role in other cell types, in human bronchial epithelial cells, STING is central to cytosolic DNA-induced MUC5AC expression, whereas IFN-β expression is dependent on RIG-I. Our data indicate a functional interaction between the STING and RIG-I pathways, suggesting the existence of intricate and cell-specific cytosolic DNA-sensing systems.
Alpha and beta glucocorticoid receptor mRNA expression in human bronchial epithelial cells
