title: 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.
abstract: 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.
authors.affiliation: Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan. hirasawa@mail.pharm.tohoku.ac.jp
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.forename: Yuhsuke
authors.initials: Y
authors.lastname: Ohsawa
authors.forename: Goh
authors.initials: G
authors.lastname: Katoh
authors.forename: Kazue
authors.initials: K
authors.lastname: Shibata
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishihara
authors.forename: Toshio
authors.initials: T
authors.lastname: Seyama
authors.forename: Soichiro
authors.initials: S
authors.lastname: Tamura
authors.forename: JangJa
authors.initials: J
authors.lastname: Hong
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohuchi
mesh_terms: 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
chemical_list: 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