Objective To elucidate the mechanism of interferon-gamma (IFN-γ) to inhibit the restenosis after successful percutaneous transluminal angioplasty (PTA).Methods A rabbit vascular restenotic model was constructed and...Objective To elucidate the mechanism of interferon-gamma (IFN-γ) to inhibit the restenosis after successful percutaneous transluminal angioplasty (PTA).Methods A rabbit vascular restenotic model was constructed and the proliferation of intimal smooth muscle cells (SMCs) were observed by monitoring their expression of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor β chain mRNA (PDGF-β mRNA) at the indicated time points. Results IFN-γ could significantly inhibit the expression of PCNA by intimal SMCs one week after denudation, when counting 200 intimal cells for PCNA-positive reactions with an inhibitory rate of 88.50% (P<0.001). IFN-γ could downregulate in situ expression of PDGF-β mRNA by these cells as we calculated the average number of PDGF-β mRNA positive cells per square millimetre area at ×400 magnification with reduced rates of 86.85% in 1 week group (P<0.001), of 93.66% in 2 week group (P<0.001) and of 52.92% in 4 week group (0.02<P<0.05), respectively. Conclusions The local production of PDGF-β by vascular intimal SMCs via an autocrine mechanism may be responsible for continuous proliferation of these cells and the formation of neointima after injury. This could be inhibited by IFN-γ through downregulating the expression of PDGF-β mRNA. These results provide an in vivo basis for IFN-γ to be used clinically for the management of restenosis after percutaneous transluminal angioplasty.展开更多
Porcine epidemic diarrhea virus（PEDV） is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PED...Porcine epidemic diarrhea virus（PEDV） is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PEDV exhibits an obvious capacity for modulating interferon（IFN） signaling or expression. The newly discovered type III IFN, which plays a crucial role in antiviral immunity, has strong antiviral activity against PEDV proliferation in IPEC-J2 cells. In this study, we aimed to investigate the effect of PEDV nucleocapsid（N） protein on type III IFN-λ. We found that the N proteins of ten PEDV strains isolated between 2013 and 2017 from different local farms shared high nucleotide identities, while the N protein of the CV777 vaccine strain formed a monophyletic branch in the phylogenetic tree. The N protein of the epidemic strain could antagonize type III IFN, but not type I or type II IFN expression induced by polyinosinic-polycytidylic acid（poly（I：C）） in IPEC-J2 cells. Subsequently, we demonstrated that the inhibition of poly（I：C）-induced IFN-λ3 production by PEDV N protein was dependent on the blocking of nuclear factor-κB（NF-κB） nuclear translocation. These findings might help increase understanding of the pathogenesis of PEDV and its mechanisms for evading the host immune response.展开更多
文摘Objective To elucidate the mechanism of interferon-gamma (IFN-γ) to inhibit the restenosis after successful percutaneous transluminal angioplasty (PTA).Methods A rabbit vascular restenotic model was constructed and the proliferation of intimal smooth muscle cells (SMCs) were observed by monitoring their expression of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor β chain mRNA (PDGF-β mRNA) at the indicated time points. Results IFN-γ could significantly inhibit the expression of PCNA by intimal SMCs one week after denudation, when counting 200 intimal cells for PCNA-positive reactions with an inhibitory rate of 88.50% (P<0.001). IFN-γ could downregulate in situ expression of PDGF-β mRNA by these cells as we calculated the average number of PDGF-β mRNA positive cells per square millimetre area at ×400 magnification with reduced rates of 86.85% in 1 week group (P<0.001), of 93.66% in 2 week group (P<0.001) and of 52.92% in 4 week group (0.02<P<0.05), respectively. Conclusions The local production of PDGF-β by vascular intimal SMCs via an autocrine mechanism may be responsible for continuous proliferation of these cells and the formation of neointima after injury. This could be inhibited by IFN-γ through downregulating the expression of PDGF-β mRNA. These results provide an in vivo basis for IFN-γ to be used clinically for the management of restenosis after percutaneous transluminal angioplasty.
基金Project supported by the National Natural Science Foundation of China(No.31702250)the Key Research and Development Project Funds of Zhejiang Provincial Science and Technology Department(Nos.2015C02044 and 2018C02028)+2 种基金the Agricultural Technology Extension Funds of Zhejiang Universitythe Dabei Agricultural Discipline Development and Talent Training Fund(No.2017ZDNT004)the Three Rural and Six Party Funds,China
文摘Porcine epidemic diarrhea virus（PEDV） is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PEDV exhibits an obvious capacity for modulating interferon（IFN） signaling or expression. The newly discovered type III IFN, which plays a crucial role in antiviral immunity, has strong antiviral activity against PEDV proliferation in IPEC-J2 cells. In this study, we aimed to investigate the effect of PEDV nucleocapsid（N） protein on type III IFN-λ. We found that the N proteins of ten PEDV strains isolated between 2013 and 2017 from different local farms shared high nucleotide identities, while the N protein of the CV777 vaccine strain formed a monophyletic branch in the phylogenetic tree. The N protein of the epidemic strain could antagonize type III IFN, but not type I or type II IFN expression induced by polyinosinic-polycytidylic acid（poly（I：C）） in IPEC-J2 cells. Subsequently, we demonstrated that the inhibition of poly（I：C）-induced IFN-λ3 production by PEDV N protein was dependent on the blocking of nuclear factor-κB（NF-κB） nuclear translocation. These findings might help increase understanding of the pathogenesis of PEDV and its mechanisms for evading the host immune response.
