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研究発表を行った学会；
・第３４回　日本分子生物学会年会
　２０１１年１２月１３日〜１６日（横浜）

タイトル；The tumor suppressor Retinoblastoma protein positively regulates innate immune receptor Toll-like receptor 3 in epithelial cells.

発表者；小山　皓介　氏
　　　（熊本大学　薬学部　創薬・生命薬科学科　遺伝子機能応用学分野　４年）
Abstract；
Tumor suppressor genes regulate the anti-viral host defense through molecular mechanisms that are as yet not well explored. Previously, we reported that the tumor suppressor p53 enhances anti-viral cytokine induction by directly trans-activating basal Toll-like receptor (TLR) 3 expression, which is the sensing receptor for viral double-stranded RNA and poly (I:C). Here we show that the tumor suppressor retinoblastoma (Rb) protein also positively regulates TLR3 expression. TLR3 expression was lower in Rb knockout (KO) murine embryonic fibroblasts (MEF) cells than in WT MEF cells. Consequently, induction of KC and beta interferon after poly (I:C) stimulation was impaired in Rb KO MEF cells. Knockdown of Rb by si-RNA decreased the TLR3 expression and poly (I:C) response in human epithelial cell lines. TLR3 promoter analysis showed that Rb modulates the transcription factor E2F1, which directly binds to E2F binding site on the proximal promoter of TLR3. Exogenous addition of E2F1 decreased TLR3 promoter activity, while Rb dose-dependently curbed the effect of E2F1. Interestingly, poly (I:C) decreased p53 but increased Rb expression, and the poly (I:C)-induced TLR3 expression was impaired in Rb KO MEF, suggesting that Rb might govern TLR3 expression after virus infection. Taken together, these data indicated that normally, the ubiquitous E2F1 suppresses TLR3 expression, but during virus infection Rb could be up-regulated which increases TLR3 expression and function. These results highlight a role of Rb in innate immune response in epithelial cells.