Cis-urocanic acid synergizes with histamine for increased PGE2 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 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.
Jaksic
A
A
Department of Microbiology & Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
Finlay-Jones
J J
JJ
Watson
C J
CJ
Spencer
L K
LK
Santucci
I
I
Hart
P H
PH
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000528:radiation effects*; D007213:Indomethacin / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology*
D006633:Histamine Antagonists; D006632:Histamine; D014560:Urocanic Acid; D015232:Dinoprostone; D007213:Indomethacin