Yong Suk Ryang

Anti-diabetic effect of alkaline-reduced water on OLETF rats.

Alkalin-reduced water (ARW) is known to exert several anti-cancer effects, as well as to scavenge reactive oxygen species (ROS) and reduce blood-glucose levels. This study was performed in order to determine the effects of ARW on the control of spontaneous diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We assigned 16 male OLETF rats (4 wk) to two groups: an experimental group, which was given ARW, and a control group, which received laboratory tap water. From week 6 to 32, the body weight, lipid composition, and glucose levels in the blood of the rats were measured. The glucose levels of both groups tended to increase. However, the ARW group’s glucose levels were significantly lower than those of the control group after 12 weeks (p<0.05). The total cholesterol and triglyceride levels in the ARW group were found to be significantly lower than those of the control group during the experimental period. These results suggest that ARW spurred the growth of OLETF rats during the growth stage, and that long-term ingestion of ARW resulted in a reduction in the levels of glucose, triglycerides, and total cholesterol in the blood.

Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKCδ/Ras cascades in HOS cells

Recently cloned leukotactin-1 (Lkn-1) that belongs to CC chemokine family has not been characterized. To understand the intracellular events following Lkn-1 binding to CCR1, we investigated the activities of signaling molecules in response to Lkn-1 in human osteogenic sarcoma cells expressing CCR1. Lkn-1-stimulated cells showed elevated phosphorylation of extracellular signal-related kinases (ERK1/2) with a distinct time course. ERK activation was peaked in 30 min and 12 h showing biphasic activation of ERK. Pertussis toxin, an inhibitor of G(i)/G(o) protein, and phospholipase C (PLC) inhibitor blocked Lkn-1-induced activation of ERK. Protein kinase C delta (PKC delta) specific inhibitor rottlerin inhibited ERK activation in Lkn-1-stimulated cells. The activities of PLC and PKC delta were also enhanced by Lkn-1 stimulation. Dominant negative Ras inhibited activation of ERK. Immediate early response genes such as c-fos and c-myc were induced by Lkn-1 stimulation. Lkn-1 affected the cell cycle progression by cyclin D(3) induction. These results suggest that Lkn-1 activates the ERK pathway by transducing the signal through G(i)/G(o) protein, PLC, PKC delta and Ras, and it may play a role for cell proliferation, differentiation, and regulation of gene expression for other cellular processes.

Suppression of ovalbumin-induced airway inflammatory responses in a mouse model of asthma by Mimosa pudica extract.

Asthma is an inflammatory airway disease. The pathogenic mechanisms of asthma include the infiltration of leukocytes and release of cytokines. Mimosa pudica (Mp) has been used traditionally for the treatment of insomnia, diarrhea and inflammatory diseases. Although Mp extract has various therapeutic properties, the effect of this extract on asthma has not yet been reported. This study investigated the suppressive effects of Mp extract on asthmatic responses both in vitro and in vivo. Mp extract was acquired from dried and powdered whole plants of M. pudica using 80% ethanol. BALB/c mice were used for the mouse model of asthma induced by ovalbumin. Mp extract significantly inhibited the HMC‐1 cell migration induced by stem cell factor and blocked the release of monocyte chemotactic protein‐1 (MCP‐1) and interleukin‐6 (IL‐6) in EoL‐1 cells. Leukocytosis, eosinophilia and mucus hypersecretion in asthmatic lung were significantly suppressed by Mp extract. The release of ovalbumin‐specific IgE in bronchoalveolar lavage fluid and serum was also decreased. Mp extract treatment resulted in no liver cytotoxicity. The Mp extract has inhibitory properties on asthma and may be used as a potent therapeutic agent for allergic lung inflammation. Copyright

Differential immune profiles following experimental Echinostoma hortense infection in BALB/c and C3H/HeN mice

Despite the increasing incidence in food-borne Echinostoma hortense infection, the underlying immune mechanism along with the clinical manifestations and the expulsion of the worms from the mucosal surfaces are not well understood. To clarify the differences in the immune mechanisms induced by E. hortense in the host, we examined the interleukin (IL)-4, IL-5, IL-12, and interferon-γ profiles and the kinetics in two genetically different mouse strains, BALB/c and C3H/HeN mice, in vivo as well as in vitro. Both the crude extract and the excretory–secretory protein prepared from E. hortense increased the mRNA and protein expressions of IL-4 and IL-5 in the splenocytes isolated from both strains of infected mice. The E. hortense recovery rate of the C3H/HeN mice was much higher than that of the BALB/c mice. When analyzing the sera from the infected BALB/c and C3H/HeN mice, the IL-5 and immunoglobulin (Ig)G1 levels in the infected BALB/c mice were significantly higher than those from the C3H/HeN mice (p < 0.05). Taken together, these results show that the BLAB/c mice with E. hortense infection are more resistant than are the C3H/HeN mice due to the significantly higher induction of protective Th2 immunity.

Immune response and inhibitory effect of ketotifen on the BALB/c and C3H/HeN mice infected with Echinostoma hortense

Although Echinostoma hortense is one of the intestinal trematodes with a high infection rate in South Korea, the exact immune response against E. hortense infection has yet to be fully investigated. In the present study, we investigated differential susceptibilities in two different strains of micenamely, BALB/c (H-2d) and C3H/HeN (H-2k) mice. Likewise, we investigated the effects of ketotifen, an antiallergic drug, on the immune response against E. hortense infection. The worm recovery rate of the C3H/HeN mice was much higher than that of the BALB/c mice. The messenger ribonucleic acid (mRNA) expressions of interleukin (IL)-4 and IL-5 in the BALB/c mice were stronger than that of the C3H/HeN mice after E. hortense infection, but IL-1β and tumor necrosis factor (TNF)-α expressions in the BALB/c mice were weaker than that of the C3H/HeN mice after E. hortense infection. The number of goblet cells and eosinophils increased after E. hortense infection in the BALB/c and the C3H/HeN mice. The worm recovery rate was higher and lasted longer in the ketotifen-treated mice in comparison to the untreated mice. Ketotifen suppressed the mRNA expression of IL-4 and IL-5 in the BALB/c mice, but did not in the C3H/HeN mice. The IL-1β expressions were inhibited by ketotifen in the two strains, but TNF-α expression was inhibited in the C3H/HeN mice after ketotifen treatment. In addition, ketotifen inhibited the increase in eosinophils and goblet cells in varying degrees, depending on the strain. In summary, the immune sensitivity against E. hortense depends on the species of the host. The ketotifen treatment administered on the infected mice differently blocked the immune response against E. hortense infection.

NF‐κB‐dependency and consequent regulation of IL‐8 in echinomycin‐induced apoptosis of HT‐29 colon cancer cells

The present study was to see whether echinomycin‐induced apoptosis would be NF‐κB‐dependent and if so, whether echinomycin would activate or inhibit NF‐κB as well as resultant chemokine IL‐8 expression. In HT‐29 cells echinomycin activated NF‐κB in time‐dependent manner. EMSA in the presence of antibodies specific for p50 and p65 subunits indicated that echinomycin‐induces the translocation of p50–p65 heterodimeric subunits of NF‐κB. Levels of IκB were detected at initial echinomycin treatment and thereafter decreased, faintly seen after a 6 h treatment. In contrast p‐IκB levels were clearly detected throughout 6–24 h of echinomycin treatment, albeit initially fainted. To clarify the role of NF‐κB on IL‐8 expression in echinomycin‐mediated apoptosis of HT‐29 cells, ELISA plus RT‐PCR clearly showed that IL‐8 production is inducible by echinomycin treatment. Using a specific inhibitor, IL‐8 regulation at echinomycin treatment in HT‐29 cells occurred via both caspase‐3 and NF‐κB‐dependent signal pathway. To confirm whether two different pathways (NF‐κB and caspase) would be coupled, only NF‐κB inhibitor (PDTC) and caspase‐3 specific inhibitor (Z‐DEVD‐FMK) together significantly attenuated echinomycin‐initiated apoptosis of HT‐29 cells, pretreatment of HT‐29 cells with PDTC rarely affected echinomycin‐induced caspase‐3 activation. So echinomycin‐induced apoptosis in HT‐29 cells occurs via NF‐κB activation independent of caspase‐3 activation modulating the resultant‐linked key chemokine IL‐8 expression and echinomycin‐induced apoptosis is NF‐κB‐dependant and directly related to NF‐κB activation, consequently regulating IL‐8 expression.