Targeting Mechanism of a Novel Liver-targeting Interferon IFN-CSP Involves Liver Heparan Sulfate Proteoglycan

Author(s): Xuemei Lu, Jie Wang, Xiaobao Jin, Yanting Huang, Wenting Zeng, Jiayong Zhu.

Journal Name: Current Drug Delivery

Volume 13 , Issue 4 , 2016

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Abstract:

Background: In our previous study, a novel liver-targeting interferon (IFN-CSP) combining IFN α2b with plasmodium region I-plus peptide was successfully designed and prepared with Escherichia coli expression systems. The purified IFN-CSP showed anti-HBV activity and liver-targeting potentiality. The present investigation was designed to investigate the molecular mechanisms responsible for liver-targeting of IFN-CSP.

Methods: The binding site of IFN-CSP in hepatocytes was assayed by immunofluorescent staining. The correspondence of HSPG distribution and the pattern of IFN-CSP binding in liver tissue were determined using a confocal laser scanning microscope. Both the hepatocytes and liver tissue were using as model to investigate the effect of enzyme and soluble glycosaminoglycan on IFN-CSP binding using flow cytometry and fluorescence microscope.

Results: Studies of hepatocytes demonstrated that the localization of IFN-CSP in hepatocytes was the plasma membrane. Studies of liver tissue slices showed that IFN-CSP bound to liver tissue in a pattern similar to the distribution of heparan sulfate proteoglycan (HSPG) immunoreactivity. Pretreatment of hepatocytes and liver slices with heparinase reduced the binding of IFN-CSP to HepG2.2.15 cells and liver slices. Coincubation of IFN-CSP with heparin markedly inhibited IFNCSP binding to HepG2.2.15 cells and liver slices.

Conclusion: These results indicate that the molecular mechanisms responsible for IFN-CSP targeting involve binding to HSPG of hepatocytes and liver.

Keywords: IFN-CSP, liver-targeting, Heparan sulfate proteoglycan.

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Article Details

VOLUME: 13
ISSUE: 4
Year: 2016
Page: [528 - 533]
Pages: 6
DOI: 10.2174/1567201812666150827123602
Price: $58

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