IL-17B Is Elevated In Patients With Pneumonia And Mediates IL-8 Production In Bronchial Epithelial Cells

Subject: Pneumonia is responsible for an inordinate disease burden in the world.There is evidence that lung tissue cells play a major role in regulating pulmonary immunity and inflammation.Among them,bronchial epithelial cells are the first defense barrier against external pathogens,and pulmonary fibroblasts are abundant in connective tissue as cellular communication-bridging interstitium and vasculature in the lung.Lung tissue cells are actively involved in innate and adaptive immune responses against lung infections through the production of proinflammatory cytokines,growth factors,chemokines and other antimicrobial substances.Knowledge about the role of lung tissue cells in pulmonary immunity and inflammation could facilitate predicting,preventing,and curing pneumonia or other respiratory diseases.Method: Collect community-acquired pneumonia(CAP)patients and normal blood samples(37 adult Pneumonia patients/ 14 Healthy controls,28 paediatric Pneumonia patients/ 14 Healthy controls),the levels of IL-17 B and IL-8 in the two groups were detected by ELISA.Q-PCR was used to detect the expression of cytokine m RNA in IL-17B-treated human bronchial epithelial cells(BEAS-2B)and human lung fibroblasts(HLF)Q-PCR.TNF-?,IFN-? alone or in combination with IL-17 B 24 hours after treatment of human bronchial epithelial cells,ELISA to detect cell culture supernatant changes in IL-8 levels.Human bronchial epithelial cells were treated with signal pathway inhibitor for 1 hour,then treated with IL-17 B for 24 hours,and the supernatant of IL-8 was detected by ELISA.IL-17 B treatment of BEAS-2B at different time points,western blot detection of intracellular signaling pathway phosphorylation level.The pneumonia model of mice was constructed with Pseudomonas aeruginosa,Staphylococcus aureus,Escherichia coli and Streptococcus pneumoniae.The levels of IL-17 B and IL-8 in bronchoalveolar lavage fluid and serum were detected by ELISA.Results: The levels of IL-17 B and IL-8 in serum of CAP patients were significantly increased and positively correlated.IL-17 B could induce the expression of IL-8 in human bronchial epithelial cells,and it was dose-dependent.TNF-? significantly enhanced IL-17B-induced BEAS-2B expression of IL-8,whereas IFN-? significantly reduced IL-17 B stimulation of BEAS-2B production of IL-8.IL-17 B stimulated human bronchial epithelial cells 5 minutes later,NF-?B,Akt,ERK,P38 MAPK phosphorylation levels were significantly increased,the levels of IL-8 in the BEAS-2B group treated with NF-?B inhibitor,Akt inhibitor,ERK inhibitor,P38 MAPK inhibitor combined with IL-17 B alone were significantly lower than those of IL-17 B alone treated group,and NF-?B,Akt,ERK,P38 MAPK phosphorylation levels were significantly reduced.The levels of IL-17 B and IL-8 in the model of pneumonia were significantly increased and the positive correlation between them.Conclusion: IL-17 B up-regulates the expression of IL-8 by activating NF-?B,Akt,ERK and P38 MAPK signaling pathways in the lungs,and further promotes the immune response.