Suppression by Azelastine Hydrochloride of NF-/.KAPPA.B Activation Involved in Generation of Cytokines and Nitric Oxide.

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Abstract
The influence of the anti-allergy agent azelastine hydrochloride (Azeptin®)on NF-κB activation associated with the. generation of cytokines and nitric oxide (NO)was investigated in various kinds of human and mouse cells. Azeptin dose-dependently suppressed both DNA and protein synthesis in human gingival fibroblasts (HF)and also suppressed blastogenesis of human peripheral blood lymphocytes (PBL). Generation of tumor necrosis factor-alpha, interleukin 1-beta, granulocyte-macrophage colony-stimulating factor and interleukin-6 from 10-5 M Azeptin-treated PBL and human monocytes (HM)was decreased to approximately 1/3 to 2/3 of the control levels. In parallel with the decreased cytokine generation, each cytokine mRNA was less expressed in the presence of 10-5 M Azeptin. In addition, both inducible nitric oxide synthase-mRNA level and NO generation in mouse peritoneal macrophages were suppressed by 10-5 M Azeptin. Being compatible with those results, Azeptin (10-5 M)suppressed activation of NF-κB in PBL, HM and HF. These results appear to indicate that suppression of cytokine and NO generation by Azeptin results at least partially from the inhibition of NF-κB activation.

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