IL-6 Antagonizes the Inhibitory Activities of TGF-beta on Dendritic Cell Maturation via Smads

• Main Authors: Mo-Fan Chen, 陳墨繁
• Other Authors: 朱瑞民
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/06525591347151956019

碩士 === 國立臺灣大學 === 獸醫學研究所 === 97 === The dendritic cell (DC) activities are significantly hampered in many cancers. It is interesting that, in a canine cancer model, canine transmissible venereal tumor (CTVT), when the cancer enters a spontaneous regression (R), the inhibited DC activities are restored. CTVT produces high levels of TGF-b However, the role of TGF-b and 5h3 mechanisms involved in the DC functional suppresion and the restoration is largely unknown. We confirmed that the CTVT-derived TGF-b suppressed monocyte-derivedDC activities. After TGF-b treatment, the T cell activation through DC was impeded and the supernatants from the progression phase CTVT that contained TGF-b. Neutralizing the TGF-b in the supernatants by specific monoclonal antibody reversed the inhibition of DC-induces lymphocyte stimulation and also enhanced the DC MHC II expression. Our precious sstudy indicated that IL-6 produces by tumor infiltrating lymphocytes in the CTVT R phase sxhibited strong anti-TGF-b activity. The recovery of the TGF-b inhibitrf DC activities by IL-6 was thereforer studied. The flow cytometry results showed a strong reaction of IL6 in restoring TGF0b0down-regulated MHC expression on DCs. We ffurther verified whether IL-6 interfered with the TGF-b activities directly. Using Western blotting and confocal microscopy, we found that the nuclear translocation of Smad2/3, a sign of signal transduction of TGF-b, was blocked by adding IL-6. The evidence that the Smad7, which is an inhibitory Smad, was not oncreased in expression by adding IL-6 indicated that the nuclear translocation of Smad2/3 blocked by IL-6 was not through Smad7 pathway. This study provides in depth understanding of the host/cancer interactions and possible applications of IL-6 to restore DC activities in cancers that produce TGF-b.