Deficiency of C-C Chemokine Receptor 5 Suppresses Tumor Development via Inactivation of NF-kappa B and Upregulation of IL-1Ra in Melanoma Model

Title
Deficiency of C-C Chemokine Receptor 5 Suppresses Tumor Development via Inactivation of NF-kappa B and Upregulation of IL-1Ra in Melanoma Model
Author(s)
최동영송주경[송주경]박미희[박미희]유환수[유환수]한상배[한상배]윤도영[윤도영]홍진태[홍진태]
Keywords
HUMAN BREAST-CANCER; CELL GROWTH; SKIN CARCINOGENESIS; IN-VIVO; INTERLEUKIN-1; ANTAGONIST; EXPRESSION; ADENOCARCINOMA; INHIBITION; CARCINOMA
Issue Date
201205
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.7, no.5
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-kappa B 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-kappa B, and translocation of p50 and p65 into the nucleus through the inhibition of phosphorylation of I kappa B was found in the melanoma tissues of CCR5(-/-) mice compared to melanoma tissues of CCR5(+/+) mice. NF-kappa B 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 cells was significantly increased in melanoma tumor and spleen tissue of CCR5(-/-) mice compared to that of CCR5(+/+) mice. Therefore, these results showed that CCR5 deficiency caused apoptotic cell death of melanoma through inhibition of NF-kappa B and upregulation of IL-1Ra.
URI
http://hdl.handle.net/YU.REPOSITORY/28286http://dx.doi.org/10.1371/journal.pone.0033747
ISSN
1932-6203
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약학대학 > 약학부 > Articles
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