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Membrane TNFα: Importance for the Effector Function of Dendritic Cells and Potential Ways of Its Targeted Modulation

Authors
  • Tyrinova, T. V.
  • Mishinov, S. V.
  • Leplina, O. Yu.
  • Dolgova, E. V.
  • Proskurina, A. S.
  • Batorov, E. V.
  • Tikhonova, M. A.
  • Kurochkina, Yu. D.
  • Oleynik, E. A.
  • Kalinovskiy, A. V.
  • Chernov, S. V.
  • Stupak, V. V.
  • Bogachev, S. S.
  • Ostanin, A. A.
  • Chernykh, E. R.
Type
Published Article
Journal
Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology
Publisher
Pleiades Publishing
Publication Date
Jul 01, 2018
Volume
12
Issue
3
Pages
247–254
Identifiers
DOI: 10.1134/S199074781803008X
Source
Springer Nature
Keywords
License
Yellow

Abstract

Membrane TNFα (mTNFα) is expressed on many immune cell types and performs various biological functions. Dendritic cells (DC) of high-grade glioma patients exhibit impaired cytotoxic activity against TNFα-sensitive HEp-2 tumor cells. The mechanisms leading to the impairment of the TNFα- dependent tumoricidal activity of DC and the possibility of regulating the cytotoxic activity of DC mediated by the TNFα/TNF-R1 signaling pathway have been studied. The study was conducted on healthy donors and patients with newly diagnosed high-grade glioma. DC were generated by culturing the plastic-adherent peripheral blood mononuclear cell fraction in the presence of GM-CSF and interferon-α (IFN-DC). It was shown that the impairment of the cytotoxic activity of patient IFN-DC was associated with a low number of DC expressing mTNFα and a low level of TNFα mRNA expression in DC. IFN-DC of patients exhibited a tendency of high activity of the TNFα-converting enzyme (TACE), which accomplishes shedding of mTNFα from the cell membrane. An increased number of IFN-DC with mTNFα caused by TACE blocking enhanced cytotoxic activity of the patient’s IFN-DC against HEp-2 cells. It was established that exogenous interleukin-2 and extracellular DNA are up-regulators of the mTNFα expression on IFN-DC of the patients, but their effects are mediated by different mechanisms.

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