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.
Hart
P H
PH
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
Jones
C A
CA
Jones
K L
KL
Watson
C J
CJ
Santucci
I
I
Spencer
L K
LK
Finlay-Jones
J J
JJ
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