Understanding the role of astrocytes and the NVU during bacterial infection

Further investigation is required to determine the exact role of astrocyte derived VEGF and other proinflammatory cytokines on BBB permeability during GBS meningitis. In summary we have demonstrated that GBS actively invades and persists in human astrocytes and that various bacterial PHA-680632 surface factors promote these interactions. Further astrocytes respond to GBS infection with a robust proinflammatory response, which may impact disease progression. Understanding the role of astrocytes and the NVU during bacterial infection will provide important information regarding BBB disruption and the development of neonatal meningitis. Chronic persistent infection in liver is one of the clinical characteristics of hepatitis C virus, frequently causing liver Diethylstilbestrol cirrhosis and hepatocellular carcinoma. Recently, in addition to the therapy of pegylated interferon plus ribavirin, emerging anti-HCV drugs are bringing about dramatic improvement for chronic hepatitis C. However, for extermination of HCV, the development of other anti-HCV drugs targeting its persistent HCV infection and a vaccine are needed. On the other hand, a hepatoma cell line, Huh7, and its subclone such as Huh7.5 are susceptible to infection with these HCV strains and have been used for in vitro experiments. However, the infected cells are unstable and eventually undergo cell death, so-called lytic infection. Although some cell lines persistently infected with HCV were reported, the periods of persistency were months. Thus, strictly speaking, they cannot be called persistent infection systems. Here, to study HCV-infected cells in a more stable condition, we firstly established a cell line persistently infected with TNS2J1. We have maintained this cell line for more than 2 years, the longest ever reported, since the initial transfection with RNA of TNS2J. It was noteworthy that this cell line displayed prominent steatosis, accumulation of lipid droplet. Clinically, chronic hepatitis C are frequently associated with steatosis.Thus, secondary, to elucidate alterations in the metabolism and gene expression underlying such steatosis, we performed integrated analyses with metabolomics and expression arrays taking advantage of the cell line established here.

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