Экспрессия генов цитокинов, антигенов дифференцировки и факторов транскрипции в дендритных клетках человека, активированных двуцепочечной ДНК

Одно из важнейших свойств экстраклеточной двуцепочечной ДНК, имеющее отношение к терапии различных заболеваний, – это ее способность через дендритные клетки (ДК) активировать эффекторные клетки иммунной системы (противоопухолевый и вакцинальный иммунитет). Стимулирующий эффект ДНК на ДК опосредуется через TLR9 сигнальный путь и/или через систему цитозольных сенсоров и проявляется усилением экспрессии МНС антигенов II класса и костимулирующих молекул, а также синтеза иммунорегуляторных цитокинов. В настоящей работе была исследована экспрессия генов цитокинов, антигенов дифференцировки и факторов транскрипции в ДК, активированных двуцепочечной ДНК человека: (1) без использования каких-либо дополнительных факторов, (2) при использовании липофильного агента и (3) при блокировании TLR9 хлорохином. Оценка эффекта ДНК проводилась после 6- и 24-часовой экспозиции. Показано, что препарат двуцепочечной ДНК при трансфекции липофектамином активирует ДК на таком же уровне, как и Poly(dA : dT), синтетический аналог двуцепочечной ДНК. Установлено, что совместная обработка ДНК и хлорохином усиливает экспрессию генов ИФН-α, ИФН-β, ИФН-γ, ИЛ­8, МСР1, VEGF, CD25 и CD83 к 24 ч инкубации. Впервые показано, что геномная «self» двуцепочечная ДНК как монопрепарат активирует синтез мРНК ИФН-α, ИФН-β, ИФН-γ, ИЛ­8, ИЛ­10 и VEGF в ДК к 6 часам индукции.

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