Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-κB and upregulation of IL-1Ra in melanoma model.

PloS One
Ju Kyoung SongJin Tae Hong

Abstract

To evaluate the relevance of C-C chemokine receptor type 5 (CCR5) expression and tumor development, we compared melanoma growth in CCR5 knockout (CCR5(-/-)) mice and wild type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced tumor volume, tumor weight, and increased survival rate when compared to CCR5(+/+) mice. We investigated the activation of NF-κB since it is an implicated transcription factor in the regulation of genes involving cell growth, apoptosis, and tumor growth. Significant inhibition of DNA binding activity of NF-κB, and translocation of p50 and p65 into the nucleus through the inhibition of phosphorylation of IκB was found in the melanoma tissues of CCR5(-/-) mice compared to melanoma tissues of CCR5(+/+) mice. NF-κB target apoptotic protein expression, such as cleaved caspase-3, cleaved PARP, and Bax, was elevated, whereas the survival protein expression levels, such as Bcl-2, C-IAP1, was decreased in the melanoma tissues of CCR5(-/-) mice. Interestingly, we found that the level of IL-1Ra, a tumor growth suppressive cytokine, was significantly elevated in tumor tissue and spleen of CCR5(-/-) mice compared to the level in CCR5(+/+) mice. Moreover, infiltration of CD8(+) cytotoxic T cell and CD57(+) natural killer ...Continue Reading

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Citations

Jan 11, 2014·Viral Immunology·Javad SanchooliDerek Kennedy
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Methods Mentioned

BETA
electromobility
fluorescence microscopy
cytokine array
electrophoresis
biopsies
flow cytometry
protein assay

Software Mentioned

WinMDI
GraphPad Prism

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