Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity

摘要

Background: Cytokines play a pivotal role in allergy development through activating signaling mechanisms, such as the Janus kinase/signal transducer and activator of transcription (STAT) pathway, which controls the expression of numerous proinflammatory genes. Objective: In comparison with 2 different corticosteroids and a calcineurin inhibitor, the efficacy of a STAT1 decoy oligodeoxynucleotide (dODN)-containing ointment on hapten-induced contact hypersensitivity was examined in 3 different animal models. Methods: After sensitization, the test compounds were administered before hapten challenge, after hapten challenge, or both to different sites of the animal skin. Subsequent erythema and edema formation was scored macroscopically, microscopically, or by a shift in ear weight. Biopsy specimens were taken and processed for histopathology, immunohistochemistry, and real-time PCR analyses. Results: Treatment with the STAT1 dODN but not the corresponding control ODN markedly improved the clinical signs ofinflammation in all 3 animal models in a dose-related manner. In guinea pig skin this was accompanied by a distinct decrease in leukocyte infiltration into the dermis after 24 hours. In addition, expression of CD40, IFN-7, IL-ip, IL-8, IL-12, and TNF-a was strongly attenuated. The dODN was equally effective in the domestic pig model when administered therapeutically, and its preventive effect in the mouse model lasted for more than 48 hours. Conclusions: Altogether, treatment with the dODN proved to be at least as effective as treatment with the reference compounds. (J Allergy Clin Immunol 2008;121:158-65.)#