Results and figures

Sarah and Waleed

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

Do PAF receptor antagonists inhibit cis-UCA induced immune suppression?

YES!

And so does the 5-HT receptor antagonist,

ketanserin!

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

Do cis-UCA and 5-HT share a receptor?

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

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-5HT2A cells

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

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

Copyright ©2006 by the National Academy of Sciences

Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425

Immunoprecipitation study

Are Cis-UCA and 5-HT structurally similar?

YES

Do cis-UCA and 5-HT share a receptor?

YESImmunoprecipitation

Does blocking 5-HT binding inhibits UV/cis-UCAinduced immunosuppression?

In vivo studies

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

Sample size?

n=5

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-UCAinduced immunosuppression?

YESIn vivo studies

Conclusions

Immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT2A receptor

Potential for using 5-HT receptor antagonists to prevent skin cancer by blocking UV-induced immune suppression, but further studies are needed.