Article

 

ColemanDanielPharmacyRetinoid-X-Receptors_SupportingInformation.zip Public Deposited

No preview available

Download the file

https://ir.library.oregonstate.edu/concern/articles/8g84mn84p

Descriptions

Attribute NameValues
Creator
Abstract
  • Understanding the molecular mechanisms of ultraviolet (UV) induced melanoma formation is becoming crucial with more reported cases each year. Expression of type II nuclear receptor Retinoid-X-Receptor α (RXRα) is lost during melanoma progression in humans. Here, we observed that in mice with melanocyte-specific ablation of RXRα and RXRβ, melanocytes attract fewer IFN-γ secreting immune cells than in wild-type mice following acute UVR exposure, via altered expression of several chemoattractive and chemorepulsive chemokines/cytokines. Reduced IFN-γ in the microenvironment alters UVR-induced apoptosis, and due to this, the survival of surrounding dermal fibroblasts is significantly decreased in mice lacking RXRα/β. Interestingly, post-UVR survival of the melanocytes themselves is enhanced in the absence of RXRα/β. Loss of RXRs α/β specifically in the melanocytes results in an endogenous shift in homeostasis of pro- and anti-apoptotic genes in these cells and enhances their survival compared to the wild type melanocytes. Therefore, RXRs modulate post-UVR survival of dermal fibroblasts in a ‘‘non-cell autonomous’’ manner, underscoring their role in immune surveillance, while independently mediating post-UVR melanocyte survival in a ‘‘cell autonomous’’ manner. Our results emphasize a novel immunomodulatory role of melanocytes in controlling survival of neighboring cell types besides controlling their own, and identifies RXRs as potential targets for therapy against UV induced melanoma.
Rights Statement
Additional Information
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2014-07-08T19:35:50Z (GMT) No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors.pdf: 15563615 bytes, checksum: c26d989981093c5b67dfd4731505da84 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors_SupportingInformation.zip: 14204479 bytes, checksum: 2d885fda83344bbb2857beca2573cc76 (MD5)
  • description.provenance : Made available in DSpace on 2014-07-08T19:35:51Z (GMT). No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors.pdf: 15563615 bytes, checksum: c26d989981093c5b67dfd4731505da84 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors_SupportingInformation.zip: 14204479 bytes, checksum: 2d885fda83344bbb2857beca2573cc76 (MD5) Previous issue date: 2014-05-08
  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2014-07-08T19:35:28Z No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors.pdf: 15563615 bytes, checksum: c26d989981093c5b67dfd4731505da84 (MD5) ColemanDanielPharmacyRetinoid-X-Receptors_SupportingInformation.zip: 14204479 bytes, checksum: 2d885fda83344bbb2857beca2573cc76 (MD5)