vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RASvavilov-258Research ArticleСтатьиArticlesДИНАМИКА ЭКСПРЕССИИ ЦИТОКИНА IL-12 В МАКРОФАГАХ ЧЕЛОВЕКА ПОСЛЕ ИХ ОБРАБОТКИ ДИОКСИНОМDYNAMICS OF IL12 CYTOKINE EXPRESSION IN HUMAN MACROPHAGES AFTER TREATMENT WITH DIOXINОщепковД. Ю.OshchepkovD. Y.diman@bionet.nsc.ruКашинаЕ. В.KashinaE. V.diman@bionet.nsc.ruАнтонцеваЕ. В.AntontsevaE. V.diman@bionet.nsc.ruОщепковаЕ. А.OshchepkovaE. A.diman@bionet.nsc.ruМордвиновВ. А.MordvinovV. A.diman@bionet.nsc.ruФурманД. П.FurmanD. P.diman@bionet.nsc.ruФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaRussian FederationФедеральное государственное бюджетное учреждение науки Институт цитологии и генетики Сибирского отделения Российской академии наук, Новосибирск, Россия Новосибирский национальный исследовательский государственный университет, Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, RussiaRussian Federation201416012015182354362Copyright © Ощепков Д.Ю., Кашина Е.В., Антонцева Е.В., Ощепкова Е.А., Мордвинов В.А., Фурман Д.П., 20152015Ощепков Д.Ю., Кашина Е.В., Антонцева Е.В., Ощепкова Е.А., Мордвинов В.А., Фурман Д.П.Oshchepkov D.Y., Kashina E.V., Antontseva E.V., Oshchepkova E.A., Mordvinov V.A., Furman D.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/258

Интерлейкин-12 (IL-12) является важнейшим провоспалительным цитокином, синтезируемым макрофагами, однако данные о влиянии диоксина на его экспрессию до сих пор фрагментарны. Наличие выявленных нами ранее потенциальных DRE (dioxin responsive elements) в регуляторных районах генов IL12A и IL12B, кодирующих субъединицы цитокина IL-12p35 и IL-12p40 соответственно, предполагает возможность прямой активации этих генов через связывание DRE с комплексом диоксин /AhR/ARNT.

В настоящей работе связывающая способность этих DRE доказана с помощью гель-шифт анализа. Исследование динамики экспрессии генов IL12A и IL12B на модели макрофагоподобных клеток человека линии U937 не выявило влияния диоксина на уровень экспрессии гена IL12A. В то же время выявлена кратковременная активация, а затем падение экспрессии гена IL12B. Наблюдаемая динамика может объясняться прямой активацией экспрессии диоксин-содержащим комплексом и последующим подавлением экспрессии в результате оксидативного стресса, вызываемого диоксином. Таким образом, известный факт влияния диоксина на иммунную систему может быть связан в том числе и с различным его влиянием на динамику экспрессии генов, кодирующих субъединицы IL-12.

Interleukin IL-12 is a key proinflammatory cytokine, synthesized by macrophages, but the information concerning the dioxin effect on its expression is still fragmentary. The presence of previously identified potential dioxin responsive elements (DREs) in the regulatory regions of IL12A and IL12B genes, encoding IL-12 subunits IL-12p35 and IL-12p40, respectively, suggests direct activation of these genes by binding of the dioxin/AhR/ARNT complex to DREs. This work proves the binding capacity of these DREs by gel shift assay. The study of the dynamics of IL12A and IL12B gene expression in the human macrophage cell line U937 revealed no influence of dioxin on IL12A expression. In contrast, activation of IL12B gene expression with subsequent inhibition was noted. The observed dynamics can be explained by direct activation of the expression by the dioxin-containing complex and subsequent inhibition of the expression because of oxidative stress caused by dioxin. Thus, the well-known dioxin influence on the immune system can be associated with the difference in the dioxin effect on the expression dynamics of the genes encoding IL-12 subunits.

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The authors declare that there are no conflicts of interest present.