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Song K.C.,Gachon University | Chang T.-S.,Center for Cell Signaling and Drug Discovery Research | Lee H.,Gachon University | Kim J.,Gachon University | And 2 more authors.
Journal of Ginseng Research

In the present study, effects of sun ginseng (SG) on the collagen synthesis and the proliferation of dermal fibroblast were investigated. Collagen synthesis was measured by assaying procollagen type I C-peptide production. In addition, the level of matrix metalloproteinase (MMP)-1 was assessed by western blot analysis. SG suppressed the MMP-1 protein level in a dose-dependent manner. In contrast, SG dose-dependently increased tissue inhibitors of MMP (TIMP)-1 production in fibroblasts. SG increased type I collagen production directly and/or indirectly by reducing MMP-1 and stimulating TIMP-1 production in human dermal fibroblasts. SG dose-dependently induced fibroblast proliferation and this, in turn, can trigger more collagen production. These results suggest that SG may be a potential pharmacological agent with anti-aging properties in cultured human skin fibroblast. © The Korean Society of Ginseng. Source

Lee W.Y.,Sungkyunkwan University | Park K.J.,Seoul National University | Cho Y.B.,Sungkyunkwan University | Yoon S.N.,University of Ulsan | And 9 more authors.
Stem Cells

Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intrale-sional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. ©C AlphaMed Press. Source

Won H.Y.,Center for Cell Signaling and Drug Discovery Research | Min H.J.,Center for Cell Signaling and Drug Discovery Research | Ahn J.H.,Korea Research Institute of Chemical Technology | Yoo S.-E.,Korea Research Institute of Chemical Technology | And 3 more authors.
Biochemical Pharmacology

The ligand-activated transcription factor, peroxisome proliferator-activated receptor (PPAR)γ, and its ligands inhibit pro-inflammatory cytokine production by immune cells, thus exerting anti-inflammatory activity. As a non-thiazolidinedione PPARγ ligand, KR62980 has anti-diabetic and anti-adipogenic activities, but its anti-inflammatory function has yet to be characterized. In this study, we investigated the functions and mechanisms of KR62980 in the activation and differentiation of CD4+ T helper (Th) cells by comparing its effects with those of a thiazolidinedione PPARγ ligand, rosiglitazone. KR62980 dose-dependently and significantly suppressed TCR-triggered Th cell proliferation by suppressing IL-2/IL-2Rα-mediated signaling. Both KR62980 and rosiglitazone suppressed IFNγ production in a dose-dependent manner, whereas IL-4 gene expression was specifically suppressed by only KR62980. In addition, sustained KR62980 treatment diminished Th2 cytokine production by inhibiting c-Maf expression. In vivo administration of KR62980 in a model of allergic asthma significantly attenuated eotaxin-induced eosinophil infiltration, allergic cytokine production and collagen deposition in the lung. KR62980 also decreased goblet cell hyperplasia in the airway and mucous cell metaplasia in nasal epithelium, concurrent with decreases of allergic Th2 cytokines and IL-17 in the draining lymph node. In conclusion, a novel PPARγ ligand, KR62980, suppresses in vitro Th2 cell differentiation and attenuates in vivo OVA-induced airway inflammation, suggesting a beneficial role for KR62980 in the treatment of allergic asthma and allergic rhinitis. © 2009 Elsevier Inc. All rights reserved. Source

Kang D.H.,Center for Cell Signaling and Drug Discovery Research | Lee D.J.,Center for Cell Signaling and Drug Discovery Research | Kim J.,Center for Cell Signaling and Drug Discovery Research | Lee J.Y.,Center for Cell Signaling and Drug Discovery Research | And 5 more authors.

BACKGROUND - : Typical 2-Cys peroxiredoxin (Prx) is inactivated by overoxidation of the peroxidatic cysteine residue under oxidative stress. However, the significance in the context of vascular disease is unknown. METHODS AND RESULTS - : Immunohistochemical analyses revealed that 2-Cys Prxs, particularly Prx type II, are heavily overoxidized in balloon-injured rodent carotid vessels and in human atherosclerotic lesions. Consistent with this observation, the selective depletion of Prx II exacerbated neointimal hyperplasia in injured carotid vessels. We also found that the epipolythiodioxopiperazine class of fungal metabolites exhibited an enzyme-like activity mimicking 2-Cys Prx peroxidase and manifestly eliminated the intracellular H2O2 in the vascular cells. Functionally, the epipolythiodioxopiperazines reciprocally regulated the platelet-derived growth factor receptor-β- and vascular endothelial growth factor receptor-mediated signaling in these vascular cells by replacing Prx II. As a consequence, the epipolythiodioxopiperazines inhibited the proliferative and migratory activities of smooth muscle cells but promoted those of endothelial cells in vitro. Moreover, administration of the epipolythiodioxopiperazines to the injured carotid vessels resulted in a successful recovery by inhibiting neointimal hyperplasia without causing cytotoxicity and simultaneously inducing reendothelialization. CONCLUSIONS - : This study reveals for the first time the involvement of the 2-Cys Prx overoxidation and thus the therapeutic use of their activity mimetic in vascular injuries like stenting. © 2013 American Heart Association, Inc. Source

Won H.Y.,Center for Cell Signaling and Drug Discovery Research | Min H.J.,Center for Cell Signaling and Drug Discovery Research | Lee W.H.,Research Institute of Pharmaceutical science | Kim S.G.,Research Institute of Pharmaceutical science | Hwang E.S.,Center for Cell Signaling and Drug Discovery Research
Biochemical and Biophysical Research Communications

G12 family have been known to modulate a variety of cellular events such as cell migration, B cell activation and maturation, cytokine production, and cell differentiation. In particular, Gα12 modulates IgG production, thus induces IgG antibody-mediated immune responses. However, it is largely unknown whether Gα12 is required for T cell-mediated immune functions. In this study, we investigated the effects of Gα12 in the activation and differentiation of CD4+ T cells. While PMA plus ionomycin induced equal levels of IL-2 production in WT and Gα12-deficient lymphocytes, TCR-triggered IL-2 production was significantly attenuated in Gα12 KO lymphocytes. In particular, CD4+ T cells and effector Th cells lacking of Gα12 revealed diminished IL-2 production, but not IFNγ production, upon TCR stimulation. In addition, supplement of IL-2 preferentially induced Gα12-deficient CD4+ T cells into Th2 and Th17 cells; however, the expression of specific transcription factors was unchanged in Gα12 KO Th cells. While IL-2 expression was still diminished by the re-stimulation with anti-CD3, PMA plus ionomycin restored IL-2 production in Gα12-deficient Th1 and Th2 cells. These results suggest that Gα12 may be a critical signaling molecule in TCR-induced IL-2 production and also relay a signal to suppress Th2 and Th17 cell differentiation. © 2010 Elsevier Inc. All rights reserved. Source

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