[Construction of adenoviral vector encoding soluble human TNFRI-IgGFc cDNA and its expression in human bronchial epithelial cells]

Nan Fang Yi Ke Da Xue Xue Bao. 2008 Apr;28(4):517-21.
[Article in Chinese]

Abstract

Objective: To construct a recombinant adenovirus vector carrying soluble extracellular region of tumor necrosis factor alpha receptor I-IgGFc (sTNFRI-IgGFc) and express the fusion protein in human bronchial epithelial HBE135-E6E7 cells.

Methods: sTNFRI-IgGFc fusion gene was subcloned into the adenovirus shuttle plasmid pDC316, which was co-transfected with helper plasmid pBHGloxPE1,3Cre into HEK293 cells. The recombinant adenovirus (Ad-sTNFRI-IgGFc) was generated by homologous recombination of the 2 plasmids in HEK293 cells. After identification with PCR, Ad-sTNFRI-IgGFc was amplified and purified, and its titer measured using TCID50 assay. The transcription and expression of sTNFRI-IgGFc gene in the transfected HBE135-E6E7 were detected by RT-PCR and immunohistochemistry.

Results: Ad-sTNFRI-IgGFc was successfully constructed with a viral titer of 3 x 10(10) TCID50/ml. The expression of sTNFRI-IgGFc mRNA and protein was confirmed in the transfected HBE135-E6E7 cells.

Conclusion: The constructed Ad-sTNFRI-IgGFc can effectively infect HBE135-E6E7 cells for efficient expression of sTNFRI-IgGFc protein, which antagonizes the cytolytic effect of TNFalpha in L929 cells, suggesting the potential of adenovirus expressing sTNFRI-IgGFc for local treatment of asthma.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Bronchi / cytology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Genetic Vectors / genetics*
  • Immunoglobulin Fc Fragments / biosynthesis
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / genetics*
  • Receptors, Tumor Necrosis Factor, Type I / biosynthesis
  • Receptors, Tumor Necrosis Factor, Type I / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Transfection

Substances

  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Fusion Proteins
  • TNFRSF1A protein, human