IL-6 Antagonizes the Inhibitory Activities of TGF-beta on Dendritic Cell Maturation via Smads
Date Issued
2009
Date
2009
Author(s)
Chen, Mo-Fan
Abstract
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.
Subjects
Monocyte-derived-DC
CTVT
SDGs
Type
thesis
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