Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression.

Histidine decarboxylase (HDC) catalyzes the formation of histamine from histidine. Histamine has various effects in physiological and pathological reactions, such as inflammation, cell growth, and neuro-transmission. We investigated the role of hypoxia-inducible factor (HIF)-1 on hypoxia-induced HDC expression in human mast cell line, HMC-1 cells and mouse bone marrow-derived mast cells (BMMCs). Hypoxia significantly increased histamine production. HDC expression and activity were induced by hypoxia. Additionally, when cells were transfected with a native form of HIF-1alpha, hypoxia could induce higher HDC expression than in the nontransfected cell. HIF-1 binding activity for HDC 5' flanking region (HFR) was similar to that for the hypoxia-responsive element. Using HDC promoter deletion analysis, we also demonstrated that HFR was regulated by HIF-1 activation. In addition, depletion of HIF-1alpha prevents hypoxic induction of HDC in BMMCs. In conclusion, these results demonstrate that hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1.

Inhibition of mast cell-mediated anaphylaxis by sochungryong-tang.

According to traditional Asian philosophy, sochungryong-tang (S-Tang) is a prescription for treating exterior syndrome. In this study, we investigated the effect of S-Tang on mast cell-mediated anaphylaxis. S-Tang completely inhibited compound 48/80-induced systemic anaphylactic shock at a dose of 100 mg/kg. When S-Tang was given as pretreatment at concentrations ranging from 1 to 1000 mg/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. S-Tang inhibited the local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody, and also inhibited the histamine release from the rat peritoneal mast cells by compound 48/80 or anti-DNP IgE. These results indicate that S-Tang may contain substances with actions that inhibit mast cell degranulation.