Modification of the picryl chloride-induced allergic dermatitis model in mouse ear lobes by 12-O-tetradecanoylphorbol 13-acetate, and analysis of the role of histamine in the modified model.
BACKGROUND
In atopic dermatitis, inflammation induced by antigen-nonspecific stimuli further enhances the allergic inflammation. However, there is no experimental model in which allergic dermatitis is evoked where the inflammation has been induced by antigen-nonspecific stimuli. Here, we established a novel dermatitis model in mice and analyzed the role of histamine.


METHODS
After sensitization with picryl chloride (PiCl) by painting on ear lobes of cyclophosphamide-treated mice, 12-O-tetradecanoylphorbol 13-acetate (TPA) was painted twice at the same site, and then allergic inflammation was induced by painting PiCl. Histamine antagonists and cyclosporine A (CsA) were administered intravenously.


RESULTS
The application of TPA shifted the PiCl-induced allergic inflammation from a delayed-type response to a biphasic response, increased the infiltration of eosinophils and mast cells at the inflammatory site, shifted the cytokine milieu from Th1 to Th2 and induced the expression of thymic stromal lymphopoietin in the ear lobes. The PiCl-induced increase in the thickness of the ear lobe in the immediate phase was suppressed by the H1 antagonist pyrilamine. In contrast, the increase in the swelling in the late phase and the infiltration of eosinophils were suppressed by the H3/H4 antagonist thioperamide. The inhibitory effect of the combined treatment with pyrilamine and thioperamide on the TPA-modified contact dermatitis was as potent as that of CsA.


CONCLUSIONS
Induction of the antigen-nonspecific inflammation by TPA enhanced the PiCl-induced allergic inflammation. Histamine plays significant roles in the early-phase swelling via H1 receptors, and the late-phase swelling via H3/H4 receptors in this TPA-modified allergic dermatitis model.
Hirasawa
Noriyasu
N
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan. hirasawa@mail.pharm.tohoku.ac.jp
Ohsawa
Yuhsuke
Y
Katoh
Goh
G
Shibata
Kazue
K
Ishihara
Kenji
K
Seyama
Toshio
T
Tamura
Soichiro
S
Hong
JangJa
J
Ohuchi
Kazuo
K
D000818:Animals; D002452:Cell Count; D002927:Cimetidine / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D054644:Ear Auricle / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006632:Histamine / Q000276:immunology*; D006633:Histamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000276:immunology*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011738:Pyrilamine / Q000494:pharmacology / Q000627:therapeutic use; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D006633:Histamine Antagonists; D010880:Piperidines; D015847:Interleukin-4; D007073:Immunoglobulin E; D002927:Cimetidine; D006632:Histamine; D007371:Interferon-gamma; D016572:Cyclosporine; D003520:Cyclophosphamide; D047209:Eosinophil Peroxidase; D011738:Pyrilamine; C052075:thioperamide; D013755:Tetradecanoylphorbol Acetate; D010853:Picryl Chloride; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse