BACKGROUND: The World Health Organization (WHO) has noted that allergic diseases are a major health problem of the 21st century. Allergic rhinitis (AR) is a type I allergic disease characterized by nasal mucosa and immune system abnormalities. AR is mediated by various inflammatory cells and is mainly characterized by altered secretion of cytokines. Thymic stromal lymphopoietin (TSLP) and the interleukin-33/stimulation-expressed gene 2 (IL-33/ST2) signaling pathway are cytokines that play pivotal roles in many inflammatory responses and allergic reactions. There have been reports of interactions between the 2 pathways in many diseases. Hypoxia is a common pathologic manifestation of AR. The aim of this study was to explore the relationship and expressions and biologic functions of TSLP and IL-33/ST2 in AR, and also to determine the effects of hypoxia on these cytokines. METHODS: The rat nasal mucosal epithelium was obtained from Wistar rats. Cells were cultured in groups under hypoxia and normoxia conditions. Identification of rat nasal epithelial cell (RNEpC) and protein expressions was done by immunohistochemistry and immunofluorescence methods. Cell proliferation and migration were examined using the cell counting kit-8 (CCK-8) and Transwell kit. Detection of apoptosis was tested using a fluorescence apoptosis kit. Enzyme-linked immunoassay (ELISA) and Western blot analysis ELISA were used to measure cell secretion and protein expressions. For these experiments, TSLP was knocked down by lentivirus transfection and IL-33 blocked with its antagonist. RESULTS: TSLP, IL-33, and ST2 expressions were significantly higher in nasal mucosa epithelial cells from AR rats than in those from control rats. Hypoxia further promoted their expression. Increased TSLP and IL-33/ST2 promoted cell proliferation, inhibited cell apoptosis, and enhanced cell migration. In addition, the downregulation of TSLP expression effectively attenuated expression of the IL-33/ST2 axis and, through use of IL-33 antagonists, could also reduce TSLP expression, a synergistic effect more obvious under hypoxia. CONCLUSION: Our data indicate that TSLP and IL-33/ST2 signaling pathways interact with each other in the pathogenesis and pathologic development of AR. TSLP inhibition is a key factor in AR treatment. Inhibiting hypoxia-induced pathologic processes could represent a therapeutic effect by inhibiting IL-33/ST2 expression via downregulating TSLP.
BACKGROUND: The World Health Organization (WHO) has noted that allergic diseases are a major health problem of the 21st century. Allergic rhinitis (AR) is a type I allergic disease characterized by nasal mucosa and immune system abnormalities. AR is mediated by various inflammatory cells and is mainly characterized by altered secretion of cytokines. Thymic stromal lymphopoietin (TSLP) and the interleukin-33/stimulation-expressed gene 2 (IL-33/ST2) signaling pathway are cytokines that play pivotal roles in many inflammatory responses and allergic reactions. There have been reports of interactions between the 2 pathways in many diseases. Hypoxia is a common pathologic manifestation of AR. The aim of this study was to explore the relationship and expressions and biologic functions of TSLP and IL-33/ST2 in AR, and also to determine the effects of hypoxia on these cytokines. METHODS: The rat nasal mucosal epithelium was obtained from Wistar rats. Cells were cultured in groups under hypoxia and normoxia conditions. Identification of rat nasal epithelial cell (RNEpC) and protein expressions was done by immunohistochemistry and immunofluorescence methods. Cell proliferation and migration were examined using the cell counting kit-8 (CCK-8) and Transwell kit. Detection of apoptosis was tested using a fluorescence apoptosis kit. Enzyme-linked immunoassay (ELISA) and Western blot analysis ELISA were used to measure cell secretion and protein expressions. For these experiments, TSLP was knocked down by lentivirus transfection and IL-33 blocked with its antagonist. RESULTS:TSLP, IL-33, and ST2 expressions were significantly higher in nasal mucosa epithelial cells from ARrats than in those from control rats. Hypoxia further promoted their expression. Increased TSLP and IL-33/ST2 promoted cell proliferation, inhibited cell apoptosis, and enhanced cell migration. In addition, the downregulation of TSLP expression effectively attenuated expression of the IL-33/ST2 axis and, through use of IL-33 antagonists, could also reduce TSLP expression, a synergistic effect more obvious under hypoxia. CONCLUSION: Our data indicate that TSLP and IL-33/ST2 signaling pathways interact with each other in the pathogenesis and pathologic development of AR. TSLP inhibition is a key factor in AR treatment. Inhibiting hypoxia-induced pathologic processes could represent a therapeutic effect by inhibiting IL-33/ST2 expression via downregulating TSLP.