H. M. Kim

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.

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.

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.

Taraxacum officinale restores inhibition of nitric oxide production by cadmium in mouse peritoneal macrophages

Nitric oxide (NO) produced at high concentrations by the inducible NO synthase is an important effector molecule involved in immune regulation and defense. The involvement of NO in the toxicity of cadmium (Cd) has been proposed. We have established that Cd inhibits the production of NO by recombinant IFN-gamma (rIFN-gamma) and lipopolysaccharide-stimulated mouse peritoneal macrophages. In the present study, we searched restoration drug against the inhibition of NO production by Cd in Oriental medicine. An aqueous extract of Taraxacum officinale (Compositae) (TOAE) restored the inhibition of NO production by mouse peritoneal macrophages pretreated with Cd in a dose-dependent manner. The effect of TOAE was mainly dependent on TOAE-induced tumor necrosis factor-alpha (TNF-alpha) secretion. These results suggest that the capacity of TOAE to restore NO production from interferon-gamma (IFN-gamma)-primed mouse peritoneal macrophages is the result of TOAE-induced TNF-alpha secretion.

p38 MAPK and NF-κB on IL-6 Release in Human Gingival Fibroblasts

The induction of interleukin-6 (IL-6) using a proinflammatory cytokine (IL-1β) was studied in human gingival fibroblasts (HGFs) in relation to p38 MAPK and NF-κB transcription factor. When added to HGFs, IL-1β had a stimulatory effect on the production of IL-6, and this effect was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release also was reduced by the addition of pyrrolidine dithiocarbamate or NF-κB SN50, which has been reported as potent NF-κB inhibitor. Both the NF-κB inhibitors in the presence of SB203580 had more inhibitory effect on IL-6 release. IL-1β stimulated NF-κB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on the NF-κB activation, and both the NF-κB inhibitors failed to reduce the p38 MAPK activation in the IL-1β-stimulated HGFs. These results strongly suggest that both p38 MAPK and NF-κB are required in IL-1β-induced IL-6 synthesis and that these two IL-1β-activated pathways can be primarily dissociated.

Regulatory Effect of Cytokine Production in Patients with Cerebral Infarction by Yulda-Hanso-Tang

Abstract Yulda-Hanso-Tang (YH-Tang) is a prescription for the Taeumin cerebral infarction (CI) patients according to Sasang constitution philosophy. Taeumin patients with CI were treated with YH-Tang during the acute stage. Clinical signs of CI disappeared markedly in about 2 weeks after oral administration of YH-Tang in all patients. The mean interleukin (IL)-2 serum levels were lower in the patients with CI than in the normal groups, whereas the mean IL-4, 1L-6 and IgE levels were significantly higher in the patients. There were no significant differences in interferon-y (IFN-γ) levels between the groups. Serum IFN-γ and IL-2 levels derived from T helper (Th)1 cells elevated significantly in the patients with CI by YH-Tang administration. Significant reduced serum levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with YH-Tang. During the period of YH-Tang administration, there were no other adverse effects. The data indicate that YH-Tang has a good CI treatment effect, and that its action may be due to regulation of cytokine production.

Theanine is a candidate amino acid for pharmacological stabilization of mast cells

The increasing occurrences of allergic disorders may be attributed to exposure to environmental factors that contribute to the pathogenesis of allergy. The health benefits of green tea have been widely reported but are largely unsubstantiated. Theanine is the major amino acid present in green tea. In this study, we investigated the role of theanine in both IgE- and non- IgE-induced allergic response. Theanine inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated passive cutaneous anaphylaxis was inhibited by the oral administration or pharmaceutical acupuncture of theanine. Histamine release from mast cells was decreased with the treatment of theanine. Theanine also repressed phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced TNF-α, IL-1β, IL-6, and IL-8 secretion by suppressing NF-κB activation. Furthermore, theanine suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. The current study demonstrates for the first time that theanine might possess mast cell-stabilizing capabilities.

Aspects of gene polymorphisms in cerebral infarction: inflammatory cytokines.

Abstract.During the last decade, a growing corpus of evidence has indicated an important role of inflammatory cytokines in the pathogenesis of cerebral lesion following stroke. Recent data suggest that genetics may in turn contribute to modulating the effects of inflammatory cytokines on cerebral infarction (CI). This paper reviews the physiologic characteristics of major inflammatory cytokines and recent research developments related to cell biology and pathobiology in CI. In particular, this review focuses on the genetic aspects of inflammatory cytokines and their implications in CI.

Placenta Hominis Protects Osteoporosis in Ovariectomized Rats

In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T4) level was stimulated in OVX rats. The extracts inhibited the T4 level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.

Proinflammatory cytokine IL-1 β polymorphisms in sudden sensorineural hearing loss

The cause and pathogenesis of sudden sensorineural hearing loss (SSNHL) remain unknown. IL-1β is one of the most powerful inflammatory cytokines. The aim of this study was to evaluate the relationships between interleukin-1 β (IL-1β) gene polymorphisms (−511 C/T and +3953 C/T) in patients with SSNHL. One hundred two patients affected by SSNHL and 595 controls were genotyped for IL-1β gene polymorphisms. The polymorphisms were analyzed by polymerase chain reaction amplification and DNA fragment separation via electrophoresis. Compared to controls, the IL-1β (+3953) T allele increased the relative risk of SSNHL in subjects with IL-1β (−511) TT genotype (p = 0.022, OR = 9.111, 95% CI = 1.441–57.618). In this study, polymorphisms in the IL-1β −511 and IL-1β +3953 loci were assessed for evidence of association with SSNHL. From this assessment, a significant difference in carriage of both the IL-1β −511 T allele and the IL-1β +3953 T allele was observed between SSNHL and controls. This suggests that the IL-1β −511 and +3953 loci may play an important role in the etiopathogenesis of SSNHL.