ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS

We have studied dose effects of several Interferon (IFN) inducers, i.e., Genfaxon (beta-1 IFN), Cycloferon and Immunomax upon expression of six genes controlling the signaling in immune pathways (TLR3, TLR4, RIG1, IRF3, IPS, B2M), by means of real-time RT-PCR, being tested with blood cells from thre...

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Autores principales: T. M. Sokolova, A. N. Shuvalov, I. M. Shapoval, Z. A. Sokolova, F. I. Ershov
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Publicado: SPb RAACI 2015
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spelling oai:doaj.org-article:f95f6d44700d42359a77ba8391da8e2d2021-11-18T08:03:44ZACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS1563-06252313-741X10.15789/1563-0625-2015-1-7-18https://doaj.org/article/f95f6d44700d42359a77ba8391da8e2d2015-03-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/802https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XWe have studied dose effects of several Interferon (IFN) inducers, i.e., Genfaxon (beta-1 IFN), Cycloferon and Immunomax upon expression of six genes controlling the signaling in immune pathways (TLR3, TLR4, RIG1, IRF3, IPS, B2M), by means of real-time RT-PCR, being tested with blood cells from three humans. It is revealed that individual cell samples showed different sensitivity to these drugs, probably, due to constitutive levels of TLR3 and TLR4 gene expression and possible connections with their immune pathology. Genfaxon at a dose of 104 ME produced potent stimulation of TLR3, TLR4, IRF3 and B2M genes in two persons. Immunomax, at a dose 0,5 unit, exhibited same effect in one case only (with Epstein-Barr virus infection). Cycloferon stimulated gene expression at much lower levels than Genfaxon in any cases. We have shown a reverse correlation between sensitivity of the cells to Immunomax, and constitutive TLR3 and TLR4 expression. The stimulatory effects of Immunomax were maximal in a person with very low TLR3/4 gene expression. Immunomax boosted the genes from several signaling pathways, including TLR3, TLR4, but genes of RIG/IPS pathway showed higher activation. Cycloferon induced gene transcription of IRF3 and B2M-receptor to higher degree, than expression of TLR3 and TLR4 genes. Hence, our data concerning Genfaxon, Immunomax and Cycloferon confirm their IFN-inducing effects upon human blood cells. The RT-PCR-based evaluation of gene expression related to signaling immune pathways in blood cell populations will enable rapid and highly specific quantitation of IFN and IFN-inducer drugs activities, thus avoiding their biological testing in long-term cell cultures.T. M. SokolovaA. N. ShuvalovI. M. ShapovalZ. A. SokolovaF. I. ErshovSPb RAACIarticleifn-inducersimmune signaling genesblood cellsImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 17, Iss 1, Pp 7-18 (2015)
institution DOAJ
collection DOAJ
language RU
topic ifn-inducers
immune signaling genes
blood cells
Immunologic diseases. Allergy
RC581-607
spellingShingle ifn-inducers
immune signaling genes
blood cells
Immunologic diseases. Allergy
RC581-607
T. M. Sokolova
A. N. Shuvalov
I. M. Shapoval
Z. A. Sokolova
F. I. Ershov
ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS
description We have studied dose effects of several Interferon (IFN) inducers, i.e., Genfaxon (beta-1 IFN), Cycloferon and Immunomax upon expression of six genes controlling the signaling in immune pathways (TLR3, TLR4, RIG1, IRF3, IPS, B2M), by means of real-time RT-PCR, being tested with blood cells from three humans. It is revealed that individual cell samples showed different sensitivity to these drugs, probably, due to constitutive levels of TLR3 and TLR4 gene expression and possible connections with their immune pathology. Genfaxon at a dose of 104 ME produced potent stimulation of TLR3, TLR4, IRF3 and B2M genes in two persons. Immunomax, at a dose 0,5 unit, exhibited same effect in one case only (with Epstein-Barr virus infection). Cycloferon stimulated gene expression at much lower levels than Genfaxon in any cases. We have shown a reverse correlation between sensitivity of the cells to Immunomax, and constitutive TLR3 and TLR4 expression. The stimulatory effects of Immunomax were maximal in a person with very low TLR3/4 gene expression. Immunomax boosted the genes from several signaling pathways, including TLR3, TLR4, but genes of RIG/IPS pathway showed higher activation. Cycloferon induced gene transcription of IRF3 and B2M-receptor to higher degree, than expression of TLR3 and TLR4 genes. Hence, our data concerning Genfaxon, Immunomax and Cycloferon confirm their IFN-inducing effects upon human blood cells. The RT-PCR-based evaluation of gene expression related to signaling immune pathways in blood cell populations will enable rapid and highly specific quantitation of IFN and IFN-inducer drugs activities, thus avoiding their biological testing in long-term cell cultures.
format article
author T. M. Sokolova
A. N. Shuvalov
I. M. Shapoval
Z. A. Sokolova
F. I. Ershov
author_facet T. M. Sokolova
A. N. Shuvalov
I. M. Shapoval
Z. A. Sokolova
F. I. Ershov
author_sort T. M. Sokolova
title ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS
title_short ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS
title_full ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS
title_fullStr ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS
title_full_unstemmed ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS
title_sort activation of genes controlling the immune signaling pathways: differential individual sensitivity of human blood cells for interferon preparations and ifn inducers
publisher SPb RAACI
publishDate 2015
url https://doaj.org/article/f95f6d44700d42359a77ba8391da8e2d
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