Toll樣受體（Toll-like receptors, TLRs）作為一類重要的模式識別受體（Pattern recognition receptors, PRRs）主要表達于巨噬細胞和樹突狀細胞（Dendritic cells, DCs）表面,選擇性地識別病原體相關分子模式（Pathogen-associated molecular patterns, PAMPs）,構成機體免疫系統(tǒng)抵御病原體入侵的第一道屏障。TLR是一類在各種生物體內高度保守的I型跨膜蛋白,目前已在哺乳動物中發(fā)現(xiàn)并克隆了12種。一旦識別了病原體中特定的分子結構,TLR就會激活其下游一系列的信號通路,活化天然免疫細胞產生炎性細胞因子和I型干擾素。TLR不僅啟動天然免疫應答,控制炎癥反應的性質、強度和持續(xù)時間,還可以通過上調DC表面的MHC II類分子和共刺激分子,促進DC的成熟,指導抗原特異的免疫應答尤其是Th1型反應的產生,調節(jié)獲得性免疫應答的強度和類型,成為連接初始免疫應答和獲得性免疫應答的橋梁。TLR信號過度活化或活化不足會導致機體功能異常和疾病的發(fā)生。許多的其他信號通路參與對TLR信號的嚴密調控。因此,對T... 

【文章來源】：中國人民解放軍海軍軍醫(yī)大學上海市 211工程院校

【文章頁數(shù)】：111 頁

【學位級別】：博士

【部分圖文】：

干擾RAW264.7細胞中CaMKII的表達能抑制LPS觸發(fā)的炎性細胞因子和I型干擾素的產生Figure1-2.SilencingofCaMKIIexpressionattenuatesTLR4-activatedproinflammatorycytokineandtypeIinterferonproductioninRAW264.7cells.

圖 1-3. 干擾小鼠腹腔巨噬細胞中 CaMKII 的表達能抑制 TLR3、4、9 促發(fā)的炎性細胞因子和 I 型干擾素的產生Figure 1-3. Silencing of CaMKII expression attenuates TLR4,9,3-activatedproinflammatory cytokine and type I interferon production in macrophages.Mouse peritoneal macrophages (4 × 105) were transfected with control small RNA (Ctrl)or CaMKII-α siRNA1. After 48 hr, cells were stimulated with 0.1 μg/ml LPS (A), 0.3μM CpG ODN (B) or 10 μg/ml Poly(I:C) (C) for the indicated time. IL-6, TNF-α orIFN-β in the supernatants was measured by ELISA. Data are shown as mean ± SD ofthree independent experiments. **, P < 0.01.

CaMKII 能消除 CaMKII-α siRNA 對 LP生的抑制α overexpression rescues CaMKII-α silenction in LPS-stimulated macrophages.d RAW264.7 cells were transfected withfter 36 hr, CaMKII-α and β-actin exprelot. Similar results were obtained in three inls (1.5 × 105) were transfected with contrAfter 36h, the cells were transfected withours later, the cells were stimulated with B) and IFN-β (C) in the supernatants wean ± SD of three independent experiments.


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