• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.441-446
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• 1994

The responsiveness of $CD8^+$ T-cell subpopulation according to serum-containing and serum-free conditions were investigated. Cells are freshly isolated from spleen of mature adult BALB/C mice between 13-20 weeks of age. $CD8^+$ T cells in serum-free conditions produce small amounts of IL-2, while significant amounts of IFNr following activation when compared the results of serum-containing conditions. These data indicate that serum-derived factors may play an important role in the alternations of $CD8^+$ T cell responsiveness.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1140-1146
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• 2004

This study was carried out to investigate the comparison of immunomodualtory effects of water-extracted Ginseng Radix(GR), Pilose Asia-bell(PA), Astragali Radix(AR), Astractylodes Rhizoma alba(AA) and Dioscoreae Rhizoma (DR). The parameter examined to assess apparent immunomodulatory effect of the water-extracted GR, PA, AR, AA and DR included the regulation of Nitric oxide (NO), the expression of Th1/Th2 type cytokine, the change of B cell phenotype. The water-extracted GR, PA, AR, AA and DR inhibited NO production and iNOS protein expression in LPS stimulated RAW 264.7 macrophage cells. In the Th1 and Th2 cytokine expression, the water-extracted GR, PA, AR, AA and DR induced IL-2 and IFNr mRNA gene expression. Therefore, it seems that the water-extracted GR, PA, AR, AA and DR have a inducing effect of Th1 type cytokines. In the Flow cytometry analysis, the water-extracted GR, PA, AR, AA and DR did not change B cell phenotype (CD45R/B220). The water-extracted GR, PA, AR, AA and DR have a reducing effect of immune suppression cause by Methotrexate (MTX), an agent of immune suppression. These results suggest that the immunomodulatory effects of the water-extracted GR, PA, AR, AA and DR may be, in part, associated with the inducing IL-2 and IFNr mRNA gene expression in and regulation of NO production in macrophage cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1000-1010
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• 2005

This study was carried out to investigate the comparison of immunomodualtory effects of water-extracted Aconiti lateralis Preparata Radix(PR), Zingiberis Rhizoma(ZR), Cinnamomi Cortex(CC) and Evodiae Fructus(EF). The parameter examined to assess apparent immunomodulatory effect of the water-extracted PR, ZR, CC and EF included the regulation of Nitric oxide (NO). Also, ZR and EF represent the expression of Th1/Th2 type cytokine, the change of B cell phenotype. The water-extracted PR, ZR, CC and EF inhibited NO production and iNOS protein expression in LPS stimulated RAW 264.7 macrophage cells. In the Th1 and Th2 cytokine expression, the water-extracted ZR and EF induced IL-2, IFNr and IL-10 mRNA gene expression. Therefore, it seems that the water-extracted ZR and EF have a inducing effect of Th1 and Th2 type cytokines. In the Flow cytometry analysis, the water-extracted ZR and EF changed B cell phenotype (CD45R/B220), did NOT in PR and CC. The water-extracted PR, ZR, CC and EF have a reducing effect of immune suppression cause by Methotrexate (MTX), an agent of immune suppression. These results suggest that the immunomodulatory effects of the water-extracted ZR and EF may be, in part, associated with the inducing IL-2 and IFNr mRNA gene expression In and regulation of NO production in macrophage cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.896-901
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• 2006

Zingiberis rhizoma(ZB) has been used to treat a various condition and disease in traditional oriental medicine. The present study was conducted to evaluate the immunomodulatory effect of aqueous-extracted ZB(ZBE) on methotrexate (MTX)-induced immune suppression in mouse spleen cells. In spleen cell proliferation assay, ZBE enhanced mitogenic activity in mouse spleen cells. In RT-PCR, ZBE induced IL-2, IFNr and IL-6 cytokine gene expression in mouse spleen cells. In spite of MTX treatment, IL-2, IFNr and IL-6 gene expressions sustained in MTX treated spleen cells. CD45R/B220, pan B marker was slightly increased in ZBE treated mouse spleen cells. IL-6, B cell tropical cytokine, production was induced by ZBE-treated mouse spleen cells and IL-6 production was sustained on MTX-ZBE co-cultured cells. ZBE administration enhanced suNival of S-180 bearing mouse. These data indicate that ZBE has a protective effect of immune suppression caused by MTX, and ZBE may be enhance cellular and humoral function by regulate cytokine gene expression as well as the mitogenic effect on spleen cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.414-424
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• 2007

Adenophorae Radix (AR), Liriopis Tuber (LT), Dendrobii Monile (DM), Polygonati Officinalis (PO), Polygonati Rhizoma (PR) have been used to treated a variety condition/diseases in traditional oriental medicine. The present study was conducted to investigate the immunmodulatory effects of the water-extracted AR, LT, DH, PO and PR. In spleen cell proliferation assay, DH was significantly enhanced mitogenic activity compared with control group. In RT-PCR, DH ad PO induced IL-2 and IFNr cytokine gene expression in mouse spleen cells. Methotrexate(MTX), immune supression agent, was significantly inhibited mouse spleen cell proliferation(1600 mg/ml). In spite of MTX treatement, DH and PO sustained the spleen cell proliferation, In the flow cytometry analysis, DH stimulated mouse spleen cells showed an increase in B-cell phenotype (CD45R/B220). The water-extracted DH and PO inhibited NO production and iNOS expression in LPS-stimulated RAW 264.7 macrophage cell. DH induced IL-2 and IFNg gene expression in human peripheral mononuclear cells. The GC-MS analysis show that the main component of water-extracted DH was b-Nitroethyl alcohol. The main components of water-extracted PO were Dipirartril-tropico, Methyl sulfoxide and Demsodrox. These data suggest that among these extracts, DH has a protective effcet of immune suppression caused by MTX. DH may be enhance cellular and humoral immune response by the regulation of cytokine gene expression, NO production and B cell production.

• Molecules and Cells
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• v.45 no.4
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• pp.257-272
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• 2022

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.