TLR激动剂imiquimod的研究进展.pptVIP

Imiquimod--a TLR7 agonist Xiaochen Yu 2013 10 21 Introduction Imiquimod was the first small molecule approved for topical use in humans that was shown to act through the Toll-like receptor (TLR) pathway. Imiquimod activates innate immune cells that express TLR7 including plasmacytoid dendritic cells (pDC), B cells and likely some monocytes. Depending on the cell type, this activation results in secretion of cytokines including interferon-α (IFN-α) and others, upregulation of costimulatory molecule expression and maturation and/or proliferation. It was first identified as a compound that has anti-viral activity in pigs infected with herpes simplex virus, and has been successfully used for the treatment of genital warts caused by human papilloma virus in the clinical. Recent study revealed it also has direct proapoptotic activity against various tumor cell populations in vitro and in vivo. the antiviral activity of imiquimod Imiquimod and its analogues have no direct in vitro antiviral activity and are not virucidal, rather the antiviral is indirect through cytokine induction and immune activation. A TLR7 inhibitor chloroquine does not restore the growth inhibition by imiquimod Imiquimod inhibits in vivo growth of prostate cancer in mice the role of imiquimod in macrophage Numerous macrophages are present in the shoulder regions of rupture-prone life threatening atherosclerotic plaques. Removal of macrophages from plaques by macrophage-specific induction of cell death could represent an attractive approach to stabilize the structure of the plaque. To initiate selective macrophage death, we examined Toll-like receptor 7 (TLR7) as a potential target, since it is expressed in macrophages but not in SMCs. TLR7 expressed in macrophages but not in SMCs imiquimod induced cell apoptosis is dependent on TLR7 imiquimod induced macrophage autophagy by TLR7 Imiquimod-induced macrophage inflammation is TLR7 dependent the role of imiquimod in