Cis‐UROCANIC ACID SYNERGIZES WITH HISTAMINE FOR INCREASED PGE₂ PRODUCTION BY HUMAN KERATINOCYTES: LINK TO INDOMETHACIN‐INHIBITABLE UVB‐INDUCED IMMUNOSUPPRESSION

Abstract— There is considerable evidence that suppression of the immune system by UVB (280–320 nm UV) irradiation is initiated by UVB‐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 E₂ (PGE₂) production in response to histamine but not UCA alone. However, cis‐UCA synergized with histamine for increased PGE₂ production by keratinocytes. cis‐urocanic acid also increased the sensitivity of keratinocytes for PGE₂ production in response to histamine. Prostaglandin E₂ from keratinocytes exposed to cis‐UCA and histamine may contribute directly, or indirectly, to the regulation of CHS responses by UVB irradiation.