cis-Urocanic acid stimulates human peripheral blood monocyte prostaglandin E₂ production and suppresses indirectly tumor necrosis factor-α 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-α 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-α production. Histamine type 1 receptor antagonists were without effect on both the cis-UCA- and histamine-induced suppression of monocyte TNF-α 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-α levels, by restricting further cytokine recruitment, may also limit the development of the inflammatory components of hypersensitivity responses.