CIS-UROCANIC ACID SYNERGIZES WITH HISTAMINE FOR INCREASED PGE(2) PRODUCTION BY HUMAN KERATINOCYTES - LINK TO INDOMETHACIN-INHIBITABLE UVB-INDUCED IMMUNOSUPPRESSION

There is considerable evidence that suppression of the immune system by UVB (280-320 nm UV) irradiation is initiated by WE-dependent isomerization of a specific skin photoreceptor, urocanic acid (UCA), from the trans to the cis form. Previous studies have confirmed that cis-UCA administration to mice 3-5 days prior to hapten sensitization at a distant site, suppresses the contact hypersensitivity (CHS) response upon challenge. This study demonstrates in mice that cis-UCA, like UVB, suppresses CHS to trinitrochlorobenzene by a mechanism partly dependent on prostanoid production. In vitro experimentation showed that human keratinocytes, isolated from neonatal foreskin, increased prostaglandin E(2) (PGE(2)) production in response to histamine but not UCA alone. However, cis-UCA synergized with histamine for increased PGE(2) production by keratinocytes. Cis-urocanic acid also increased the sensitivity of keratinocytes for PGE(2) production in response to histamine. Prostaglandin E(2) from keratinocytes exposed to cis-UCA and histamine may contribute directly, or indirectly, to the regulation of CHS responses by UVB irradiation.