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作 者:Feifei Qi Yiwei Yan Qi Lv Mingya Liu Ming Liu Fengdi Li Ran Deng Xujian Liang Shuyue Li Guocui Mou Linlin Bao
机构地区:[1]Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases,NHC Key Laboratory of Comparative Medicine,Institute of Laboratory Animal Science,CAMS&PUMC,Beijing,China [2]National Center of Technology Innovation for Animal Model,Beijing,China [3]State Key Laboratory of Respiratory Health and Multimorbidity,Beijing,China
出 处:《Animal Models and Experimental Medicine》2025年第3期483-492,共10页动物模型与实验医学(英文)
基 金:the National Natural Science Foundation of China,Grant/Award Number:32000358;the CAMS initiative for Innovative Medicine of China,Grant/Award Number:2021-I2M-1-035;Young Elite Scientists Sponsorship Program by CAST(YESS),Grant/Award Number:2020QNRC001。
摘 要:Background:The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus(MERS-CoV)infection,thereby providing a novel therapeutic strategy for managing the clinical treatment of inflammatory response caused by respiratory virus infection.Methods:We investigated the development of MERS by infecting hDPP4 mice with hCoV-EMC(107 TCID50[50%tissue culture infectious dose])intranasally.We infected A549 cells with MERS-CoV,which concurrently interfered with IL-37,detecting the viral titer,viral load,and cytokine expression at certain points postinfection.Meanwhile,we administered IL-37(12.5μg/kg)intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5 days after infection to investigate the efficacy of IL-37 in MERS-CoV infection.Results:The viral titer of MERS-CoV-infected A549 cells interfering with IL-37 was significantly reduced by 4.7-fold,and the viral load of MERS-CoV-infected hDPP4 mice was decreased by 59-fold in lung tissue.Furthermore,the administration of IL-37 suppressed inflammatory cytokine and chemokine(monocyte chemoattractant protein 1,interferon-γ,and IL-17A)expression and ameliorated the infiltration of inflammatory cells in hDPP4 mice.Conclusion:IL-37 exhibits protective properties in severe pneumonia induced by MERS-CoV infection.This effect is achieved through attenuation of lung viral load,suppression of inflammatory cytokine secretion,reduction in inflammatory cell infiltration,and mitigation of pulmonary injury.
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