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.

Lung malignancy is a major cause of human mortality. As such, safe pharmacological agents that can detect lung cancer are urgently required. Magnolol has been reported to have anticancer property. However, it is still unclear whether magnolol induces apoptosis of lung carcinoma cells. In this study, magnolol inhibited cell growth, increased lactate dehydrogenase release, and modulated cell cycle in human lung carcinoma A549 cells. Magnolol induced the activation of caspase-3 and cleavage of Poly-(ADP)-ribose polymerase, and decreased the expression level of nuclear factor-κB/Rel A in the nucleus. In addition, magnolol inhibited basic fibroblast growth factor-induced proliferation and capillary tube formation of human umbilical vein endothelial cells. These data indicate that magnolol is a potential candidate for treating of human lung carcinoma.

The inflammatory processes are orchestrated by inflammatory cells through a complex set of chemical signals and can arise in any tissue in response to traumatic, infectious, postischemic, toxic, allergic, or auto-immune injury. 1) In chronic inflammatory diseases, the injury persists and leads to tissue damage.1) During inflammation, the inflammatory region is infiltrated with mononuclear cells, producing a range of inflammatory mediators, including inflammatory cytokines. 2)Mast cells are widely distributed in the connective tissues of mammals and other vertebrates, where they are frequently located in close proximity to blood vessels.3) Mast cells are important effecter cells in allergic reactions as well as in inflammatory processes due to their ability to secrete numerous cytokines. 4,5) In view of such findings, the versatile role played by mast cells is now recognized, especially in allergic inflammation.6,7) Activated mast cells can produce histamine, as well as a wide variety of other inflammatory mediators such as eicosanoids, proteoglycans, proteases, and several proinflammatory and chemotactic cytokines such as tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-4, IL-6, IL-8, IL-13, and transforming growth factor (TGF)-b1. [8][9][10] Notably, modulation of the production of cytokines from mast cells can provide a useful therapeutic strategy for allergic inflammatory disease.In recent years, cyclooxygenase (COX)-2 plays important roles in various tumors and inflammatory diseases.11) COX-2, one of the major mediators of the inflammatory reactions, is also strongly induced in activated monocytes and macrophages. Several recent studies demonstrated that prostaglandin D2 (PGD2), the COX-2 metabolite released from activated mast cells, is also essential for the pathogenesis of eosinophilic airway inflammations.12) Previously, it has been reported that COX-2 inhibitors abolished the PGD2 synthesis and attenuated eosinophils accumulation in the airway's inflammations. 13)Corydalis heterocarpa has been used traditionally to treat the boil or dysentery as well as a poison in Korea. In this study, Columbianetin was isolated from Corydalis heterocarpa but its molecular mechanisms are not well understood. Ng et al., reported that Columbianetin inhibited lipid peroxidation in brain and kidney homogenates.14) It has been reported that one of the active compounds from roots of Angelica pubescens, Columbianetin acetate, significantly demonstrated anti-inflammatory and analgesic activities.15) Kang and Kim, reported that columbianetin-O-beta-D-glucopyranoside exhibited significant neuroprotective activities against glutamate-induced toxicity. 16)To investigate the effect of Columbianetin on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore-induced cytokine production in the present study, we analyzed the production of IL-1b, IL-6, IL-8, and TNF-a on the Columbianetin treated human mast cell line, HMC-1. We also investigated the COX-2 expression by Columbianetin.Our results revealed that Columbianetin, the...

These results indicate that libanlibanoridin may be helpful in regulating mast cell-mediated allergic inflammatory response.

Ailanthus altissima swingle (ailanthic cortex, AAS) has been used as a traditional medicine for fever, bleeding, infection, and inflammation for many years in Korea. However, its mechanisms have not been examined. In the present study, we investigate the effect of AAS on the mast-cell-mediated allergic and inflammatory reaction using in vivo and in vitro models and elucidate its molecular mechanisms. AAS significantly inhibited compound 48/48-induced edema and systemic anaphylaxis. AAS significantly inhibited passive cutaneous anaphylaxis. AAS inhibited histamine release from rat peritoneal mast cells (RPMCs) in a dose-dependent manner. Moreover, AAS significantly inhibited production of inflammatory cytokines, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 on the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells. AAS inhibits the IgE or stem cell factor-induced TNF production on RPMCs. In activated HMC-1 cells, the expression level of NF-kappaB/Rel A protein increased in the nucleus, whereas the level of NF-kappaB/Rel A in the nucleus was decreased by AAS treatment. In addition, AAS inhibited the PMACI-induced IkappaBalpha degradation. In conclusion, the present results indicate that AAS has potent anti-anaphylactic and anti-inflammatory properties.