Jae-Gyun Jeong

Electrotransfer of human IL-1Ra into skeletal muscles reduces the incidence of murine collagen-induced arthritis

It has previously been demonstrated that high levels of gene expression in skeletal muscles can be achieved after direct in vivo electrotransfer of naked plasmid DNA. The purpose of this study is to examine the potential of in vivo electroporation of plasmid DNA encoding human IL‐1Ra for the prevention of murine collagen‐induced arthritis (CIA).

Uptake of Taurine and Taurine Chloramine in Murine Macrophages and their Distribution in Mice with Experimental Inflammation

Taurine is an abundant amino acid in inflammatory cells, where it acts as a trap for toxic hypochlorous acid (HOCl/OCl−) and protects tissue from damage resulting from overt inflammatory reactions as demonstrated in vivo and in vitro models of inflammation7,10,11. High concentrations of taurine are present in the cytosol of leukocytes (20–50 mM)4,8. Under physiological conditions the formation of taurine chloramine (Tau-Cl) is catalyzed by a reaction of the polymorphonuclear leukocytes (PMN) derived from myeloperoxidase (MPO) and hypochlorous acid with taurine. Formation of Tau-Cl may also be catalyzed directly by a halide-dependent myeloperoxidase reaction not involving formation of HOCl/OCl−. Although Tau-Cl inherently possesses oxidative potential, it is more stable and less toxic than HOCl. The addition of exogenous taurine strongly enhances chloramine formation. Tau-Cl plays a role in inflammation by inhibiting the production of nitric oxide, TNF-α, IL-1, IL-6, IL-8 and prostaglandin E2 in macrophages and production of superoxide anion (O2−) in PMN7,10,11,12

Effective suppression of nitric oxide production by HX106N through transcriptional control of heme oxygenase-1

Heme oxygenase-1 (HO-1) has been suggested to be a key neuroprotective enzyme because of its widespread distribution in the brain as well as its strong antioxidative effects. HX106N, a water-soluble botanical formulation, has previously been demonstrated to prevent amyloid β-induced memory impairment and oxidative stress in mice by upregulating HO-1 levels. In this study, the underlying molecular mechanisms of HX106N-induced HO-1 expression were investigated using BV-2 cells, a murine microglial cell line, and primary microglia. Treatment with HX106N induced the expression of HO-1 at the transcriptional level through the stress-responsive element-containing enhancer present in the ho-1 promoter. Nuclear factor E2-related factor 2 (Nrf2) was activated in cells treated with HX106N. The results from knockdown assay showed that small interfering RNA of Nrf2 attenuated HX106N-mediated HO-1 expression. Pharmacological inhibitors of p38 and JNK mitogen-activated protein kinases suppressed the HX106N-mediated induction of HO-1. The NF-κB signaling pathway was activated by HX106N and played a role in HX106N-induced HO-1 expression. Furthermore, HO-1 and one of its by-products during the enzymatic degradation of heme, CO, were found to be involved in HX106N-mediated suppression of NO production. Taken together, these data indicate that HX106N exerts potent antioxidative effects by increasing the expression of HO-1 through multiple signaling pathways, leading to the suppression of NO production.