Activation of the IL-10 gene promoter following photodynamic therapy of murine keratinocytes.
Photodynamic therapy (PDT), an anticancer treatment modality, has recently been shown to be an effective treatment for several autoimmune disease models including antigen-induced arthritis. PDT was found to induce the expression of IL-10 messenger RNA (mRNA) and protein in the skin, and this expression has similar kinetics to the appearance of PDT-induced suppression of skin-mediated immune responses such as the contract hypersensitivity (CHS) response. Some aspects of the UVB-induced suppression of the immune response have been linked to the induction of IL-10. IL-10 has been shown to inhibit the development and activation of Th1 cells, which are critical for many cell-mediated immune responses, including CHS. We have examined the effect of PDT and UVB irradiation on the activity of the IL-10 gene promoter and on IL-10 mRNA stability using the murine keratinocyte line, PAM 212. In vitro PDT induces IL-10 mRNA and protein expression from PAM 212 cells, which can be correlated with an increase in AP-1 DNA binding activity and activation of the IL-10 gene promoter by PDT. Deletion of an AP-1 response element from the IL-10 gene promoter was shown to abrogate the PDT-induced promoter activity indicating that the AP-1 response element is critical to IL-10 induction by PDT. In addition, PDT results in an increase in IL-10 mRNA stability, which may also contribute to the increased IL-10 expression in PAM 212 cells following PDT. In vitro UVB irradiation also results in activation of the IL-10 promoter. However, in contrast to PDT, UVB-induced activation of the IL-10 promoter is not AP-1 dependent and did not increase IL-10 mRNA stability.
Gollnick
S O
SO
PDT Center, Roswell Park Cancer Institute, Elm and Carlton St., Buffalo, NY 14263, USA. sandra.gollnick@roswellpark.org
Lee
B Y
BY
Vaughan
L
L
Owczarczak
B
B
Henderson
B W
BW
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D010778:Photochemotherapy; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
D017931:DNA Primers; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016753:Interleukin-10