Cis-urocanic acid stimulates human peripheral blood monocyte prostaglandin E2 production and suppresses indirectly tumor necrosis factor-alpha levels.
Photoisomerization of trans-urocanic acid (UCA) in the stratum corneum has been implicated in the immunosuppression detected after irradiation with UVB (UV wavelength of 280-320 nm). In this study, cis-urocanic acid suppressed human monocyte production of TNF-alpha by a PGE2-dependent mechanism. This contrasted with the mechanism involving histamine type 2 receptors by which the UCA structural analogue, histamine, suppressed monocyte TNF-alpha production. Histamine type 1 receptor antagonists were without effect on both the cis-UCA- and histamine-induced suppression of monocyte TNF-alpha levels. As indomethacin can reverse UVB-immunosuppression in murine models, we may have identified one of the cellular mechanisms responsible for reduced delayed-type hypersensitivity responses. Decreased TNF-alpha levels, by restricting further cytokine recruitment, may also limit the development of the inflammatory components of hypersensitivity responses.
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
P H
PH
Hart
C A
CA
Jones
K L
KL
Jones
C J
CJ
Watson
I
I
Santucci
L K
LK
Spencer
J J
JJ
Finlay-Jones
D001977:Brompheniramine / Q000494:pharmacology; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004155:Diphenhydramine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D015290:Second Messenger Systems; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014560:Urocanic Acid / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D000242:Cyclic AMP; D014560:Urocanic Acid; D001977:Brompheniramine; D011738:Pyrilamine; D015232:Dinoprostone