Suppression by azelastine hydrochloride of NF-kappa B activation involved in generation of cytokines and nitric oxide.
The influence of the anti-allergy agent azelastine hydrochloride (Azeptin) on NF-kappa B 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-kappa B 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-kappa B activation.
Yoneda
K
K
Department of Oral Surgery, Kochi Medical School, Japan.
Yamamoto
T
T
Ueta
E
E
Osaki
T
T
D001993:Bronchodilator Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010793:Phthalazines / Q000494:pharmacology*; D014176:Protein Biosynthesis; D015533:Transcriptional Activation / Q000187:drug effects*
D001993:Bronchodilator Agents; D016207:Cytokines; D006634:Histamine H1 Antagonists; D016328:NF-kappa B; D010793:Phthalazines; D009569:Nitric Oxide; D004247:DNA; C020976:azelastine