期刊文献+
共找到2篇文章
< 1 >
每页显示 20 50 100
SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration
1
作者 Jian-Bang Xu Wei-Jie Guan +12 位作者 Yi-Lin Zhang zhuo-er qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-Yun Zhou Jie Sheng Lei Zhao Yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2024年第4期1745-1759,共15页
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway inflammation.The envelope(E)protein,a core virulence structural component of coronaviruses,may p... Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway inflammation.The envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this process.Pathogens could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)signaling.However,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be elucidated.Here,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial barrier.In addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial cells.This elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein.Overall,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection. 展开更多
关键词 AIRWAY INFLAMMATION ELEVATED
原文传递
SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl^(−) accumulation in respiratory epithelium 被引量:3
2
作者 Lei Chen Wei-Jie Guan +15 位作者 zhuo-er qiu Jian-Bang Xu Xu Bai Xiao-Chun Hou Jing Sun Su Qu Ze-Xin Huang Tian-Lun Lei Zi-Yang Huang Jincun Zhao Yun-Xin Zhu Ke-Nan Ye Zhao-Rong Lun Wen-Liang Zhou Nan-Shan Zhong Yi-Lin Zhang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2022年第8期3080-3092,共13页
SARS-CoV-2,the culprit pathogen of COVID-19,elicits prominent immune responses and cytokine storms.Intracellular Cl^(−)is a crucial regulator of host defense,whereas the role of Cl^(−)signaling pathway in modulating p... SARS-CoV-2,the culprit pathogen of COVID-19,elicits prominent immune responses and cytokine storms.Intracellular Cl^(−)is a crucial regulator of host defense,whereas the role of Cl^(−)signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear.By using human respiratory epithelial cell lines,primary cultured human airway epithelial cells,and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge,we demonstrated that SARS-CoV-2 nucleocapsid(N)protein could interact with Smad3,which downregulated cystic fibrosis transmembrane conductance regulator(CFTR)expression via microRNA-145.The intracellular Cl^(−)concentration([Cl^(−)]i)was raised,resulting in phosphorylation of serum glucocorticoid regulated kinase 1(SGK1)and robust inflammatory responses.Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation.Moreover,N protein promoted a sustained elevation of[Cl^(−)]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4(PDE4).Rolipram,a selective PDE4 inhibitor,countered airway inflammation by reducing[Cl^(−)]i.Our findings suggested that Cl^(−)acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection.Targeting the Cl^(−)signaling pathway might be a novel therapeutic strategy for COVID-19. 展开更多
关键词 INFLAMMATION RESPIRATORY EPITHELIUM
原文传递
上一页 1 下一页 到第
使用帮助 返回顶部