Stimulation of Langerhans cells with ketoprofen plus UVA in murine photocontact dermatitis to ketoprofen.
BACKGROUND
Ketoprofen (KP) clinically evokes the allergic type of photocontact dermatitis when applied to the skin and irradiated with ultraviolet A (UVA). We have established a murine model of photocontact dermatitis to KP, which is a T cell-mediated delayed type hypersensitivity.


OBJECTIVE
To further explore the mechanism underlying this sensitivity, we investigated whether KP plus UVA activates the antigen-presenting ability of Langerhans cells (LCs).


METHODS
We analyzed the expression of surface molecules on LCs in the murine epidermis treated with KP plus UVA by immunohistochemistry and flow cytometry. Changes in the cytokine expression of epidermal cells from KP-phototreated skin were also examined by real-time PCR.


RESULTS
LCs became larger after treatment with KP plus UVA. The number of LCs was significantly decreased 2-3 days after KP phototreatment and recovered on day 5. A flow cytometric analysis revealed that KP plus UVA increased the percentage of LCs that highly expressed MHC class II, CD86, CD80, CD54 and CD40, whereas neither KP nor UVA alone enhanced the expression. KP phototreatment augmented the expression of I-A and CD86 on LCs in KP and UVA dose-dependent manners. A real-time PCR analysis of KP-phototreated skin showed that the expression of mRNA for IL-1alpha and GM-CSF was immediately increased after treatment.


CONCLUSIONS
A photosensitizing regimen of KP plus UVA activates LCs at least partly by stimulating keratinocytes to produce cytokines. Two strains of mice (BALB/c and AKR) differ in responsiveness to KP and the difference is not related to the activation of keratinocytes.
Atarashi
Kenji
K
Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan. Kenji_Atarashi@hisamitsu.co.jp
Kabashima
Kenji
K
Akiyama
Katsuhiko
K
Tokura
Yoshiki
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D051940:B7-2 Antigen / Q000378:metabolism; D017454:Dermatitis, Photoallergic / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D007660:Ketoprofen / Q000633:toxicity*; D007801:Langerhans Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology / Q000473:pathology; D013045:Species Specificity; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D053582:Interleukin-1alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007660:Ketoprofen