Skin application of the nonsteroidal anti-inflammatory drug ketoprofen downmodulates the antigen-presenting ability of Langerhans cells in mice.
BACKGROUND
Ketoprofen (KP) is widely used as a topical nonsteroidal anti-inflammatory drug that inhibits prostaglandin (PG) biosynthesis. As PGE(2) upregulates the antigen-presenting activity of Langerhans cells (LCs), i.e. migration to lymph nodes and expression of immunocompetent molecules, modulation of LC functions resulting from topical application of KP is an issue to be clarified.


OBJECTIVE
To investigate the in vivo effect of KP application to the skin and the in vitro effect of KP addition to the culture on the antigen-presenting ability of murine LCs. Methods Ears of BALB/c mice were painted with picryl chloride (PCl) hapten, KP or both. An immunofluorescence study of epidermal sheets and a flow cytometric analysis of epidermal cell suspensions from the treated ears were performed.


RESULTS
PCl altered the morphology of LCs and reduced their number, and simultaneous application of 10% KP maintained LC morphology and number. KP at 5% or 10% clearly decreased the PCl-augmented expression of major histocompatibility complex class II and CD86 on LCs. In cultivation of freshly isolated epidermal cells, 5 mmol L(-1) KP inhibited the culture-promoted expression of these molecules on LCs, whereas 100 micromol L(-1) indomethacin was not inhibitory. The further addition of PGE(2) to the KP-containing epidermal cell culture did not restore the expression of these molecules. Moreover, topical application of 10% KP to the sensitizing sites suppressed the development of contact hypersensitivity to PCl.


CONCLUSIONS
KP may have the potential to inhibit the antigen-presenting ability of LCs, in a PGE(2)-independent manner.
Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanish-Ku, Kitakyushu, Kitakyushu, Fukuoka 807-8555, Japan. kenji_atarashi@hisamitsu.co.jp
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K
Atarashi
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Kabashima
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K
Akiyama
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Y
Tokura
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017951:Antigen Presentation / Q000187:drug effects*; D051940:B7-2 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000517:prevention & control; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007660:Ketoprofen / Q000494:pharmacology* / Q000627:therapeutic use; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010853:Picryl Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051940:B7-2 Antigen; D000949:Histocompatibility Antigens Class II; D007660:Ketoprofen; D015232:Dinoprostone; D010853:Picryl Chloride