ДИНАМИКА ЭКСПРЕССИИ ЦИТОКИНА IL-12 В МАКРОФАГАХ ЧЕЛОВЕКА ПОСЛЕ ИХ ОБРАБОТКИ ДИОКСИНОМ

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.

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