Jae-Young Um

Epigallocatechin-3-Gallate Inhibits Secretion of TNF-α, IL-6 and IL-8 through the Attenuation of ERK and NF-κB in HMC-1 Cells

Background: Epigallocatechin-3-gallate (EGCG) is a major form of tea catechin and has a variety of biological activities. In the present study, we investigated the effect of EGCG on the secretion of TNF-α, IL-6 and IL-8, as well as its possible mechanism of action by using the human mast cell line (HMC-1). Methods: EGCG was treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187). To investigate the effect of EGCG on PMA+A23187-stimulated HMC-1 cells, ELISA, Western blot analysis, electrophorectic mobility shift assay and luciferase assay were used in this study. Results: EGCG (100 µM) inhibited PMA+A23187-induced TNF-α, IL-6 and IL-8 expression and production. EGCG inhibited the intracellular Ca2+ level. EGCG attenuated PMA+A23187-induced NF-ĸB and extracellular signal-regulated kinase (ERK1/2) activation, but not that of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. Conclusion: EGCG inhibited the production of TNF-α, IL-6 and IL-8 through the inhibition of the intracellular Ca2+ level, and of ERK1/2 and NF-ĸB activation. These results indicate that EGCG may be helpful in regulating mast-cell-mediated allergic inflammatory response.

Anti-Inflammatory Activity of Hyperoside Through the Suppression of Nuclear Factor-κB Activation in Mouse Peritoneal Macrophages

Hyperoside (quercetin-3-O-galactoside) is a flavonoid compound mainly found in the herb plants Hypericum perforatum L and Crataegus pinnatifida. Although hyperoside has a variety of pharmacological effects including anti-viral, anti-oxidative, and anti-apoptotic activities, the anti-inflammatory mechanism of hyperoside in mouse peritoneal macrophages remains unclear. In this study, hyperoside was shown to exert an anti-inflammatory action through suppressed production of tumor necrosis factor, interleukin-6, and nitric oxide in lipopolysaccharide-stimulated mouse peritoneal macrophages. The maximal inhibition rate of tumor necrosis factor-α, interleukin-6, and nitric oxide production by 5 μM hyperoside was 32.31 ± 2.8%, 41.31 ± 3.1%, and 30.31 ± 4.1%, respectively. In addition, hyperoside inhibited nuclear factor-κB activation and IκB-α degradation. The present study suggests that an important molecular mechanism by hyperoside reduces inflammation, which might explain its beneficial effect in the regulation of inflammatory reactions.

Alginic acid has anti-anaphylactic effects and inhibits inflammatory cytokine expression via suppression of nuclear factor-kappaB activation.

Background Alginic acid is comprised of complex polymerized polysaccharides, and can be chemically extracted from seaweed. Alginic acid has an inhibitory effect on histamine release, but its molecular mechanisms are not well understood.

The Beneficial Effect of Vanillic Acid on Ulcerative Colitis

Vanillic acid, an oxidized form of vanillin, is a benzoic acid derivative used as a flavoring agent. The objective of this study was to determine whether vanillic acid has beneficial effects against dextran sulfate sodium (DSS)-induced ulcerative colitis. Our results showed that vanillic acid reduced the severity of the clinical signs of DSS-induced colitis, including weight loss and shortening of colon length, and the disease activity index. The results of this study showed that vanillic acid significantly suppressed the expression of cyclooxygenase-2 and the activation of transcription nuclear factor-κB p65 in DSS-treated colon tissues. In addition, we observed that the plasma levels of interleukin (IL)-6 were higher in the DSS-treated group than in the control group, but these increased levels were reduced by the administration of vanillic acid. Taken together, these findings suggest that vanillic acid has a beneficial effect on DSS-induced ulcerative colitis, thereby indicating its usefulness in the regulation of chronic intestinal inflammation.

The Protective Mechanism of Antioxidants in Cadmium-Induced Ototoxicity in Vitro and in Vivo

Background Several heavy metals have been shown to have toxic effects on the peripheral and central auditory system. Cadmium (Cd2+) is an environmental contaminant showing a variety of adverse effects. Given the current rate of release into the environment, the amount of Cd2+ present in the human body and the incidence of Cd2+-related diseases are expected to increase. Objective The overall aim of this study was to gain further insights into the mechanism of Cd2+-induced ototoxicity. Methods Cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cytochrome c (cyt c), phosphorylated extracellular signal-regulated protein kinase (p-ERK), caspases, morphologic change, and functional changes in HEI-OC1 cells, rat cochlear explants, and mouse cochlea after Cd2+ exposure were measured by flow cytometry, immunohistochemical staining, Western blot analysis, and auditory brainstem response (ABR) recording. Mechanisms underlying Cd2+ototoxicity were studied using inhibitors of different signaling pathways, caspases, and antioxidants. Results Cd2+ exposure caused cell death, ROS generation, MMP loss, cyt c release, activation of caspases, ERK activation, apoptosis, and finally auditory threshold shift. Cd2+ toxicity interfered with inhibitors of cellular signaling pathways, such as ERK and c-jun N-terminal kinase, and with caspase inhibitors, especially inhibitors of caspase-9 and caspase-3. The antioxidants N-acetyl-l-cysteine and ebselen showed a significant protective effect on the Cd2+ toxicity. Conlcusions Cd2+ is ototoxic with a complex underlying mechanism. However, ROS generation may be the cause of the toxicity, and application of antioxidants can prevent the toxic effect.

Inhibitory effects of Rumex japonicus Houtt. on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

Background  Rumex japonicus Houtt. (RJH) is one of the herbs used in Eastern countries for the treatment of atopic dermatitis (AD). It has been shown to have an antioxidative effect in human skin disease.

Association of interleukin-1 alpha gene polymorphism with cerebral infarction

Interleukin-1 (IL-1) has pleiotropic actions in the central nervous system. During the last decade, a growing corpus of evidence has indicated an important role of this cytokine in the development of brain damage following cerebral ischemia. The expression of IL-1 in the brain is dramatically increased during the early and chronic stage of infarction. The IL-1 gene cluster on chromosome 2q14 contains three related genes (IL1alpha, IL1beta, and IL1 receptor antagonist) located within a 430-kb region. T and C alleles exist for the IL-1alpha-889 regulatory region and the TT genotype has been reported to increase the production of the protein in lipopolysaccharide (LPS)-stimulated mononuclear cells from IL-1alpha-889 TT carriers. We examined whether the IL-1alpha polymorphism affects the probability of cerebral infarction (CI). We genotyped 360 CI patients and 519 healthy controls for the same polymorphism. A significant increase was found for the IL-1alpha T allele in CI patients compared with controls (chi2=5.026, P=0.025). We conclude that the IL-1alpha-889 polymorphism is a major risk factor for CI in Koreans.

Vanillic acid inhibits inflammatory mediators by suppressing NF-κB in lipopolysaccharide-stimulated mouse peritoneal macrophages

Vanillic acid is a benzoic acid derivative that is used as a flavoring agent. It is an oxidized form of vanillin. At present, the mechanisms by which vanillic acid exerts its anti-inflammatory effects are incompletely understood. In this study, we attempted to determine the effects of vanillic acid on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. Our findings indicate that vanillic acid inhibits LPS-induced production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. During the inflammatory process, the levels of cyclooxygenase (COX)-2 and nitric oxide (NO) increased in mouse peritoneal macrophages, but vanillic acid suppressed both the enhanced levels of COX-2 and the production of prostaglandin E2 and NO. Moreover, vanillic acid suppressed the activation of nuclear factor-kappa B (NF-κB) and caspase-1. These results provide novel insights into the pharmacological actions of vanillic acid and are indicative of the potential use of this molecule in the treatment of inflammatory diseases.

Anti-inflammatory activity of chrysophanol through the suppression of NF-κB/caspase-1 activation in vitro and in vivo.

Chrysophanol is a member of the anthraquinone family and has multiple pharmacological effects, but the exact mechanism of the anti-inflammatory effects of chrysophanol has yet to be thoroughly elucidated. In this study, we attempted to determine the effects of chrysophanol on dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of this study demonstrated that chrysophanol effectively attenuated overall clinical scores as well as various pathological markers of colitis. Additionally, chrysophanol inhibited the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and the expression of cyclooxygenase (COX)-2 levels induced by LPS. We showed that this anti-inflammatory effect of chrysophanol is through suppression of the activation of NF-kappaB and caspase-1 in LPS-stimulated macrophages. These results provide novel insights into the pharmacological actions of chrysophanol as a potential molecule for use in the treatment of inflammatory diseases.

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

Abstract.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-1α, 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-1α prevents hypoxic induction of HDC in BMMCs. In conclusion, these results demonstrate that hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1.