Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Differential induction of inflammatory cytokines by dendritic cells treated with novel TLR-agonist and cytokine based cocktails: targeting dendritic cells in autoimmunity. | Jensen and Gad Journal of Inflammation 2010 7 37 http content 7 1 37 JOURNAL OF INFLAMMATION RESEARCH Open Access Differential induction of inflammatory cytokines by dendritic cells treated with novel TLR-agonist and cytokine based cocktails targeting dendritic cells in autoimmunity Simon S Jensen1 Monika Gad2 Abstract Background Dendritic cells DC are main gate-keepers of the immune system bridging the innate and adaptive immune system. DCs are able to mature into inflammatory DCs at sites of inflammation in both autoimmune and allergic disease thereby sustaining a continuous activation of the adaptive immune system at sites of inflammation. This function of DCs makes them attractive target cells for therapeutic intervention in inflammatory diseases. We have designed a DC-based screening model by which drug candidates can be evaluated for their ability to suppress DC maturation into an inflammatory and disease promoting phenotype. Methods Human monocyte derived DCs were differentiated using IL-4 and GM-CSF to immature DCs imDCs . The imDCs were treated with various combinations of TLR-agonists and pro-inflammatory cytokines to identify cocktails with ability to mature imDCs into inflammatory DCs. The effect of the cocktails on DC maturation was evaluated using ELISA and cytokine arrays to measure secreted cytokines and chemokines. FACS analysis was used to assess expression of maturation markers and functional studies were carried out using naive allogeneic T-cells to assay for a Thl-promoting DC phenotype. Results Nine cocktails were designed with potent ability to induce secretion of the Thl-promoting cytokines IL-12p70 and TNFa from imDCs and three were able to induce the Th17-promoting cytokine IL-23. The cocktails were further characterized using cytokine arrays showing induction of inflammation related cytokines and chemokines like CXCL10 CCL2 CCL4 CCL8 CCL15 CCL20 and IL-8 of which some are present in a range of autoimmune .
