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Results and Figures

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  • 1. Results and figures Sarah and Waleed
  • 2. PAF receptor antagonist inhibited UV-induced skin cancer induction in mice Mice without PAF antagonist developed many tumours Mice with PAF antagonist developed fewer tumours (P<0.001 Mann-Whitney U-test) Ulrich S. (2007); Molecular Carcinogenesis 46: 629-33
  • 3. Do PAF receptor antagonists inhibit cis-UCA induced immune suppression? YES! And so does the 5-HT receptor antagonist, ketanserin!
  • 4. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 PAF and serotonin receptor antagonists block cis-UCA- induced immune suppression * denotes P<0.001 PAF receptor antagonists
  • 5. Do cis-UCA and 5-HT share a receptor?
  • 6. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 5-HT and cis-UCA share binding sites
  • 7.  
  • 8. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 Saturation binding of cis-UCA to L-NCG-5HT 2A cells
  • 9. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 cis-UCA activates intracellular calcium flux via the serotonin receptor
  • 10. Are Cis-UCA and 5-HT structurally similar? YES Do cis-UCA and 5-HT share a receptor? Competitive Binding Studies /Calcium Mobilization Immunoprecipitation YES
  • 11. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 Immunoprecipitation study
  • 12. Are Cis-UCA and 5-HT structurally similar? YES Do cis-UCA and 5-HT share a receptor? YES Immunoprecipitation Does blocking 5-HT binding inhibits UV/cis-UCA induced immunosuppression? In vivo studies
  • 13. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 Inhibition of cis-UCA- and UV-induced immune suppression with selective 5-HT receptor antagonists, anti-cis-UCA antibody, or anti-5-HT antibody *denotes P<0.01
  • 14. Sample size? n=5
  • 15. Are Cis-UCA and 5-HT structurally similar? YES Do cis-UCA and 5-HT share a receptor? YES Does blocking 5-HT binding inhibits UV/cis-UCA induced immunosuppression? YES In vivo studies
  • 16. Conclusions
    • Immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT 2A receptor
    • Potential for using 5-HT receptor antagonists to prevent skin cancer by blocking UV-induced immune suppression, but further studies are needed.

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