title: Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of dinitrofluorobenzene-induced atopic dermatitis.
abstract: Tacrolimus (FK506) and cyclosporine A (Cys A) are immunosuppressive drugs used in the treatment of inflammatory diseases and for preventing rejection of allogeneic transplants. Tacrolimus forms a complex with FK506 binding protein (FKBP), and Cys A forms a complex with cyclophilin. These tacrolimus-FKBP and Cys A-cyclophilin complexes interact with calcineurin (CaN), thereby suppressing activation of T cells. In contrast, steroidal anti-inflammatory drugs suppress the immune system mainly via inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and the activating protein-1 (AP-1) pathway. Previously, we reported that tacrolimus, but not dexamethasone, reduced scratching behavior in a murine model of atopic dermatitis. To elucidate the mechanism involved in the inhibition of scratching behavior, we used a mouse model of allergic dermatitis to compare the characteristics of tacrolimus and Cys A treatment. We found that Cys A suppressed scratching behavior induced by application of 2,4-dinitrofluorobenzene, as did tacrolimus. In addition, both drugs attenuated increases in vascular permeability and scratching behavior induced by passive cutaneous anaphylaxis. These results indicate that inhibition of the CaN pathway plays an important role in tacrolimus- and Cys A-induced inhibition of scratching behavior in mice. Furthermore, we observed that CaN inhibitors suppressed mast cell-dependent allergic reaction.
authors.affiliation: Gifu Pharmaceutical University, Mitahorahigashi, Gifu 502-8585, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yamashita
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ito
authors.forename: Hideo
authors.initials: H
authors.lastname: Kato
authors.forename: Shusei
authors.initials: S
authors.lastname: Asai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D065095:Calcineurin Inhibitors; D002199:Capillary Permeability / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004139:Dinitrofluorobenzene; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis; D011537:Pruritus / Q000517:prevention & control; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000982:Antipruritics; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004139:Dinitrofluorobenzene; D016559:Tacrolimus