Tacrolimus (FK-506) is a

calcineurin inhibitor that was d

Tacrolimus (FK-506) is a

calcineurin inhibitor that was developed especially for the treatment of AD [17]. The immunosuppressive action of tacrolimus was found to be T cell specific, because it did not inhibit B cells, natural killer cells or various bone marrow-derived cell lines [18]. It also inhibits the production of several proinflammatory CX-4945 cost cytokines such as IL-3, IL-4, IL-5, IFN-γ, tumour necrosis factor-α and granulocyte/macrophage colony-stimulating factor [19]. In NC/Nga mice, tacrolimus inhibited the spontaneous dermatitis and was effective against established dermatitis by suppressing T cells, eosinophils, mast cells, IL-4, IL-5 and IgE [20, 21]. In a study on patients with AD, concomitant treatment with tacrolimus and another immunosuppressive agent was proven superior to monotherapy with either of the agents in improving overall dermatological scores [22]. Current treatments for severe AD are not always effective, and therefore, alternative therapies that are more effective need to be identified. The present study investigated the therapeutic potential of glucosamine and tacrolimus in combination on AD by an in vivo experiment performed using Df-induced dermatitis in NC/Nga mice, which is histologically and clinically similar to AD in humans [23], and determined its underlying therapeutic mechanisms. Animals.  Eight-week-old male NC/Nga

mice purchased Galunisertib molecular weight from Shizuoka Laboratory Animal Center (Hamamatsu, Japan) were included in the study. The mice were maintained under uncontrolled conventional

air conditions in the Laboratory Animal Facilities at the Dongguk University School of Medicine. The animal care and use committee of the research institute at Dongguk University Hospital approved all IKBKE described studies. Drugs and reagents.  Glucosamine was purchased from Sigma-Aldrich Co. (St. Louis, MO, USA). Tacrolimus (FK-506) was kindly provided by Chong Kun Dang pharma Inc. (Seoul, Korea). Df body ointment was prepared by Biostir Inc. (Kobe, Japan), and 1 g of Df body ointment contained 136.4 mg protein, 234 μg Der f 1 and 7 μg Der f 2. Induction of AD in NC/Nga mice.  Induction of AD using Df body ointment was performed as described previously [24]. The hair on the back of the NC/Nga mice was shaved using an electric shaver, followed by treatment with a skin-hair remover (Niclean, Ildong, Korea). Barrier disruption was achieved by 4% sodium dodecyl sulphate treatment on the shaved dorsal skin and both surfaces of each ear 3 h before the Df body ointment (100 mg/mouse) application. These procedures were repeated twice a week for 4 weeks. Scoring of skin lesion.  The extent of (1) erythema/haemorrhage, (2) scarring/dryness, (3) oedema and (4) excoriation/erosion was scored as 0 (none), 1 (mild), 2 (moderate) and 3 (severe). The total skin score was defined as the sum of individual scores [25]. The administration of drugs on Df-induced NC/Nga mice.

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