Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse bone marrow-derived dendritic cells (BMDC), with cells that had been cocultured (1:5, tumor:BMDC) with mouse ovarian surface epithelial cell line (1D8) cells, with irradiated (50Gy) 1D8 cells, or with the supernatent from 1D8 cells (25%, v/v)


ABSTRACT: The Suppressor of cytokine signaling (SOCS) family of negative regulatory proteins are upregulated in response to several cytokines and pathogen-associated molecular patterns (PAMPs), and suppress cellular signaling responses by binding receptor phosphotyrosine residues. Exposure of bone marrow-derived dendritic cells (BMDCs) to 1D8 cells, a murine model of ovarian carcinoma, suppresses their ability to express CD40 and stimulate antigen specific responses in response to PAMPs, and in particular to poly I: C with the upregulated SOCS3 transcript and protein levels. The ectopic expression of SOCS3 in both the macrophage cell line RAW264.7 and BMDCs decreased signaling in response to both poly I:C and IFNα. Further, knockdown of SOCS3 transcripts significantly enhanced the responses of RAW264.7 and BMDCs to both poly I: C and IFNα. Immunoprecipitation and pull-down studies demonstrate that SOCS3 binds to the IFNα receptor TYK2. Since poly I: C triggers autocrine IFNα signaling, binding of SOCS3 to TYK2 may thereby suppress the activation of BMDCs by polyI:C and IFNα. Thus, elevated levels of SOCS3 in tumor-associated DCs may potentially resist the signals induced by TLR3 ligands and type I interferon to decrease DC activation via binding with IFNα receptor TyK2. Experiment Overall Design: Microarray analysis was used to compare the expression levels of Control mouse bone marrow-derived dendritic cells (BMDC), with cells that had been cocultured (1:5, tumor:BMDC) with mouse ovarian surface epithelial cell line (1D8) cells, with irradiated (50Gy) 1D8 cells, or with the supernatent from 1D8 cells (25%, v/v). Experiment Overall Design: One biologic sample was analyzed for each condition, four samples in all.

ORGANISM(S): Mus musculus

SUBMITTER: Rongcun Yang 

PROVIDER: E-GEOD-10741 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tumor-induced suppressor of cytokine signaling 3 inhibits toll-like receptor 3 signaling in dendritic cells via binding to tyrosine kinase 2.

Zeng Bin B   Li Haijie H   Liu Yu Y   Zhang Zhuohan Z   Zhang Yuan Y   Yang Rongcun R  

Cancer research 20080701 13


The suppressor of cytokine signaling (SOCS) family of negative regulatory proteins is up-regulated in response to several cytokines and pathogen-associated molecular patterns (PAMP) and suppresses cellular signaling responses by binding receptor phosphotyrosine residues. Exposure of bone marrow-derived dendritic cells (BMDC) to 1D8 cells, a murine model of ovarian carcinoma, suppresses their ability to express CD40 and stimulate antigen-specific responses in response to PAMPs and, in particular,  ...[more]

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