Effect of Danchunwhangagam on LPS or DFX-induced cytokine production in peripheral mononuclear cells of cerebral infarction patients

The Danchunwhangagam (DCWGG) has long been used for various cerebrovascular diseases. However, little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to investigate the effect of DCWGG on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the lipopolysaccaride (LPS)- or desferrioxamine (DFX)-treated cells compared with unstimulated cells. We showed that DCWGG inhibited the production of TNF-alpha, IL-1alpha, IL-1beta IL-6, and IL-8 induced by LPS in a dose-dependent manner. Also, DCWGG inhibited TNF-alpha, IL-1alpha, IL-beta, IL-6, and IL-8 production-induced DFX in dose-dependent manner. These results suggest that DCWGG might have regulatory effects on LPS- or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.     

Chronic rhinosinusitis: an enhanced immune response to ubiquitous airborne fungi

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the United States. The etiology of CRS is unknown, and no effective treatment has been established. OBJECTIVE: We investigated the hypothesis that abnormal immunologic responses to ubiquitous airborne fungi contribute to the pathogenesis of this disease. METHODS: The proliferative and cytokine responses of PBMCs to extracts from 4 common airborne fungi-including Alternaria , Aspergillus , Cladosporium , and Penicillium -were examined by in vitro culture. Serum specimens were tested for specific IgE and IgG to these fungi. RESULTS: PBMCs from approximately 90% of the patients with CRS, but not those from normal individuals, produced both IL-5 and IL-13 when exposed to Alternaria. Furthermore, PBMCs from patients with CRS produced significantly more IFN-gamma than PBMCs from normal individuals in response to Alternaria (median, 553 pg/mL vs 98 pg/mL; P < .01). Levels of serum IgG antibodies to Alternaria and Cladosporium were clearly increased in patients with CRS compared with normal individuals ( P < .01). Less than 30% of the patients with CRS had specific IgE antibodies to Alternaria or Cladosporium. The increased humoral (serum IgG) response strongly correlated with the increased cellular (IL-5 production) response to Alternaria ( r = 0.619; P < .01). CONCLUSION: Patients with CRS show exaggerated humoral and cellular responses, both T(H)1 and T(H)2 types, to common airborne fungi, particularly Alternaria. The anomalous immune and inflammatory responses to ubiquitous fungi may explain the chronicity of airway inflammation in CRS.     

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. CONCLUSIONS: 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.     

Glechoma hederacea inhibits inflammatory mediator release in IFN-gamma and LPS-stimulated mouse peritoneal macrophages

Glechoma hederacea (GH) is an herb widely used herb medicine for the treatment of a variety of pathologies. In this study, the effect of GH on interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS)-induced production of nitric oxide (NO), interleukin (IL)-12p70, IL-12p40, tumor necrosis factor-alpha (TNF-alpha), and IL-6 were examined using mouse peritoneal macrophages. GH inhibits IFN-gamma/LPS-induced NO in a dose-dependent manner. The decrease in NO synthesis was reflected as a decreased amount of inducible NO synthase protein. We also found that GH inhibits pro-inflammatory cytokine, IL-12p70, and TNF-alpha production. However, GH increased IFN-gamma/LPS-induced IL-12p40 production. GH doesn't affect the IL-6 production. These findings mean that GH can be used in controlling macrophages mediated inflammation related disease.     

Vascular endothelial growth factor is regulated by hypoxic stress via MAPK and HIF-1 alpha in the inner ear

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The iron-chelator desferrioxamine (DFX) increased the expression of hypoxia-inducible factor (HIF)-1alpha in the hair cell line, HEI-OC1. The increased VEGF production by DFX was inhibited by iron. DFX also induced the activation of mitogen-activated protein kinase (MAPK) on HEI-OC1. The increased VEGF production by DFX was inhibited by a specific inhibitor of MAPK. In addition, DFX induced the VEGF production and HIF-1alpha stabilization in vivo. These results indicate that VEGF production is regulated via MAPK and HIF-1alpha under hypoxic condition in the inner ear.     

Inhibition of the stem cell factor-induced migration of mast cells by dexamethasone

Mast cell accumulation can be causally related to several allergic inflammations. Previous work has demonstrated that glucocorticoids decreased tissue mast cell number, and stem cell factor (SCF)-induced migration of mast cells required p38 MAPK activation. In the present study we investigated the effects of dexamethasone on SCF-induced migration of rat peritoneal mast cells (RPMCs). SCF significantly induced the migration of RPMCs at 4 h. Dexamethasone dose-dependently inhibited SCF-induced migration of RPMCs (approximately 90.1% at 100 nM; P < 0.05). The MAPK p38 inhibitor SB203580 (20 microM) also inhibited the SCF-induced migration. The ability of SCF to enhance morphological alteration and filamentous actin formation was also abolished by treatment with dexamethasone. Dexamethasone inhibited SCF-induced p38 MAPK activation to near-basal levels and induced MAPK phosphatase-1 expression. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with dexamethasone or SB203580 (P < 0.01). Our results show that dexamethasone potently regulates SCF-induced migration, p38 MAPK activation, and inflammatory cytokine production through the expression of MKP-1 protein in RPMCs. Such modulation may have functional consequences during dexamethasone treatment, especially mast cell-mediated allergic inflammation disorders.     

Decrease of immobility behavior in forced-swimming test and immune system enhancing effect of traditional medicine Gamisipjundaebo-tang

Gamisipjundaebo-tang (GSDBT) has been used for the purpose of development of physical strength. In the present study, we investigated the immune enhancing effect induced by GSDBT. We investigated the anti-immobility effect of GSDBT via a forced-swimming test and blood biochemical parameters related to fatigue, glucose, blood urea nitrogen, lactic dehydrogenase, creatine kinase, and total protein. GSDBT (0.1 and 1 g/kg) was orally administered to mice for 14 days. After 7 and 14 days, as assessed through a forced-swimming test, immobility time was decreased in the GSDBT-administrated group (0.1 and 1 g/kg) in comparison with the control group. In addition, after 8 days, the contents of glucose and lactate dehydrogenase in the blood serum were increased, and contents of blood urea nitrogen were decreased in the GSDBT-administrated group. After 15 days, the contents of glucose were increased, and the contents of lactate dehydrogenase and blood urea nitrogen were decreased in the GSDBT-administrated group. However, it had no effect on the elevation of creatine kinase and total protein level. We also investigated the effect of GSDBT on the production of cytokines in human T-cell line, MOLT-4 cells, and splenocytes. GSDBT significantly increased interferon (IFN)-gamma and interleukin (IL)-2 levels compared with the media control but did not affect IL-4. GSDBT increased the protein expression of IFN-gamma in MOLT-4 cells. These results suggest that GSDBT may be useful in immune function improvement and may also have antifatigue properties.     

Rubus croceacanthus Leveille inhibits mast cell-mediated anaphylactic-like reaction and tumor necrosis factor-alpha secretion

This work aims at examining the effect of the concentrated methanol extract of Rubus croceacanthus Leveille (RCL) on mast cell-mediated anaphylactic-like reaction in a murine model. RCL inhibited compound 48/80-induced systemic anaphylactic-like reaction. When RCL was given as pre-treatment at concentrations ranging from 0.01 to 1 mg/ml, the histamine release from rat peritoneal mast cells induced by compound 48/80 or anti-dinitrophenyl (DNP) immunoglobulin E (IgE) was reduced in a dose-dependent manner. RCL also inhibited passive cutaneous anaphylaxis activated by anti-DNP IgE. In addition, RCL inhibited phorbol 12-myristate 13-acetate and A23187-induced tumor necrosis factor-alpha secretion from human mast cell line HMC-1 cells. These results indicate that RCL may possess a strong anti-anaphylactic activity.