769 Interleukin-10 enhances DNA damage in human melanocytes

      Ultraviolet B (UVB) radiation-induced DNA damage is a potent trigger for immunosuppression and the subsequent development of skin cancer, including melanoma. UVB generally causes DNA damage via formation of cyclobutane pyrimidine dimers (CPD). The cytokine IL-10 has been shown to be a potential mediator of UVB-induced immunosuppression. Another cytokine, IL-23, has been identified as an antagonist of UVB-induced immunosuppression via induction of DNA repair. Previous studies showed reduced CPD formation in murine keratinocytes after treatment with IL-23. In our current study, we investigated the role of these cytokines via treatment of recombinant forms in normal human melanocytes (NHM) (MatTek Corporation) exposed to UVB radiation (150mJ/cm2). First, we determined the expression of IL-10 receptor (IL-10R), IL-12R and IL-23R on melanocytes by flow cytometry. Both IL-10R and IL-23R were expressed on melanocytes, but IL-12R was not. Next, we assessed DNA damage by CPD immunostaining. rIL-10 treatment led to a 29% increase in CPD-positive cells after UVB radiation (p<0.01). Treatment with rIL-23 in UVB-irradiated melanocytes showed no significant difference. These results suggest that IL-10 may adversely affect in melanocytes and possibly promote UV-induced melanoma development.