SARS-CoV S protein induces chemokine IP-10 expression in airway epithelial cells / 中国病理生理杂志

ABSTRACT

AIM: To investigate the molecular mechanism by which the SARS-CoV S protein induces chemokine IP-10 in airway epithelial cells.METHODS: cDNA microarrays were used to screen the gene expression profiles of human bronchial epithelial cells(16HBEs) stimulated by SARS-CoV S protein.In addition,RT-PCR,EMSA,and Western blotting were performed to analyze the phosphorylation of JAK/STAT signal pathway.The changes of IRF-1 and IP10 gene expression and the influence by the corresponding inhibitors were analyzed.RESULTS: IRF-1,a key transcription factor of the JAK/STAT signal pathway,was activated in human bronchial epithelial cells after stimulation by the S protein of SARS-CoV.The IP-10 gene expression was detected 2 h following the phosphorylation of STAT1 after 15 min,which was blocked by STAT1or JAK2 inhibitors.Electrophoretic mobility shift assay(EMSA) demonstrated that the nuclear proteins bound to ISRE and GAS but not NF-?B DNA motif.CONCLUSION: The SARS-CoV S protein induces IP-10 gene expression in human bronchial epithelial cells through activation of the JAK/STAT signal pathway,suggesting that the JAK/STAT signal pathway activated by virus plays key roles in virus infection related acute lung injury.