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


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Аннотация

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.

Авторлар туралы

T. Tyrinova

Scientific Research Institute of Fundamental and Clinical Immunology

Хат алмасуға жауапты Автор.
Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099

S. Mishinov

Scientific Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivian

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630091

O. Leplina

Scientific Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099

E. Dolgova

Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630090

A. Proskurina

Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630090

E. Batorov

Scientific Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099

M. Tikhonova

Scientific Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099

Yu. Kurochkina

Scientific Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099

E. Oleynik

Scientific Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099

A. Kalinovskiy

Federal Neurosurgical Center

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630087

S. Chernov

Federal Neurosurgical Center

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630087

V. Stupak

Scientific Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivian

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630091

S. Bogachev

Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630090

A. Ostanin

Scientific Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099

E. Chernykh

Scientific Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru
Ресей, Novosibirsk, 630099


© Pleiades Publishing, Ltd., 2018

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