Prostaglandin E2 is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors

Kenji Kabashima, Miyako Nagamachi, Tetsuya Honda, Chikako Nishigori, Yoshiki Miyachi, Yoshiki Tokura, Shuh Narumiya

    Research output: Contribution to journalArticle

    59 Scopus citations

    Abstract

    Keratinocytes are the major target of sunlight, and they produce prostaglandin (PG) E2 upon ultraviolet (UV) exposure. Although indomethacin, one of cyclooxygenase inhibitors, is known to suppress UV-induced acute skin inflammation, it remains uncertain whether endogenous PGE2 is responsible for UV-induced skin inflammation, and which subtype of PGE 2 receptors mediates this process. UV-induced skin inflammation was investigated by using genetically and pharmacologically PGE2 receptor-deficient mice. We applied UV-induced skin inflammation model to genetical and pharmacological PGE2 receptor-deficient mice. We exposed UVB on these mice at 5 kJ/m2, and examined the ear swelling and the histological findings. We also measured the blood flow using a laser doppler device to assess the intensity of UVB-induced inflammatory change. The UV-induced ear swelling at 48 h after exposure was significantly reduced in EP2-/-, EP4-/- or wild-type mice treated with the EP4 antagonist compared to control mice. Consistently, inflammatory cell infiltration into the local skin, and local blood flow after UV exposure were significantly reduced by EP2 or EP4 signaling blockade. These data suggest that PGE2-EP2/EP4 signaling is mandatory in UV-induced acute skin inflammation, presumably by enhancing blood flow in the microenvironment.

    Original languageEnglish (US)
    Pages (from-to)49-55
    Number of pages7
    JournalLaboratory Investigation
    Volume87
    Issue number1
    DOIs
    StatePublished - Jan 16 2007

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    Keywords

    • EP2
    • EP4
    • PGE
    • Skin inflammation
    • Ultraviolet
    • Vasodilatation

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine
    • Molecular Biology
    • Cell Biology

    Cite this

    Kabashima, K., Nagamachi, M., Honda, T., Nishigori, C., Miyachi, Y., Tokura, Y., & Narumiya, S. (2007). Prostaglandin E2 is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors. Laboratory Investigation, 87(1), 49-55. https://doi.org/10.1038/labinvest.3700491