Study On IL-36-driven Expression Of IL-6 And CXCL8 In Human Lung Tissue Cells

Subject: Pneumonia is an inflammation caused by different pathogens or physicochemical factors.Before the advent of antibiotics,the mortality rate was as high as 1/3.With the development of medical and scientific technology and the use of antibiotics,pneumonia can still cause about 1.4 million children ‘ s death every year.When inflammation occurs in the respiratory tract,lung tissue cells may participate in innate immunity or adaptive immune responses by secreting or regulating cytokines,inflammatory mediators,and the like.The IL-1 family is a central mediator of innate immunity and inflammation which plays a key role in a variety of local and systemic inflammatory diseases.The novel cytokines IL-36?,IL-36?,and IL-36? are members of the IL-36 family.A large number of studies have shown that the IL-36 family plays an important role in many inflammatory diseases,such as psoriasis,but the research in respiratory inflammation is rarely reported.Therefore,how the lung tissue cells should respond to IL-36?,IL-36?,IL-36? when lung get infectious and their regulatory mechanisms,are expected to provide a new direction for the targeted treatment and prognosis of pneumonia.Method: Lung tissue cells were cultured in vitro: bronchial epithelial cells(HBEC)and lung fibroblasts(HLF).The expression of IL-36 R in cells was detected by gene amplification;Q-PCR and ELISA techniques were used to detect the expression of inflammatory factors and protein secretion of HBEC and HLF under the effects of IL-36?,IL-36? and IL-36?.After IL-36 R was reversely inhibited by IL-36 Ra,the changes of related factors were observed after IL-36?,IL-36? and IL-36?'s stimulation on HBEC and HLF cells.Using signal pathway inhibitors,ELISA and Western blot to analyze and verify the signaling pathways of IL-36?,IL-36? and IL-36? involving in the regulation of inflammation-related factors.Result: IL-36 R can be stably expressed by HBEC and HLF cells.Treat HBEC and HLF cells with IL-36?,IL-36?,and IL-36? could significantly increase the expression of IL-6 and CXCL8,and the protein levels were also significantly up-regulated in a dose-time-dependent manner.The phosphorylation levels of P38 MAPK,ERK,and Akt signaling pathways were significantly enhanced in the first 5 or 15-minutes' stimulation of HBEC and HLF cells by IL-36?,IL-36?,and IL-36?.IL-36 Ra can downregulate the effects of IL-36 s on IL-6 and CXCL8,as well as the pretreatment of P38 MAPK,ERK and Akt signaling pathway inhibitors.Conclusion: IL-36?,IL-36? and IL-36? can up-regulate the expression of IL-6 and CXCL8 in HLF and HBEC through the activation of P38 MAPK,ERK,and Akt signaling pathways,which suggests a novel targeted therapy of pneumonia.