Immunoregulatory Abnormalities of T Cells and Hyperreactivity of B Cells in the In Vitro Immune Response in Pristane-Induced Lupus Mice

채병숙,신태용 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.2

Systemic lupus erythematosus (SLE) is characterized by overactive B cells that differentiate into autoantibody-forming cells, aberrant T cell function that provides helping B cells produce autoantibodies, and overproduction of proinflammatory cytokines. However, immunodysregulation in lupus pathogenensis remains incomplete. We examined mitogen-stimulated production of proinflammatory cytokines, cell proliferation, T cell activation, and T cell apoptosis in vitro in pristane-induced lupus BALB/c mice compared to normal mice. LPS-stimulated production of IL-6 and IL-10 by splenocytes and macrophages from pristane-induced lupus mice were remarkably up-regulated compared to normal mice, whereas production of macrophage TNF-α was significantly down-regulated. Moreover, in vitro production of IL-2, IL-6, IL-10 and IFN-γ by Con A-stimulated splenocytes, cell proliferation in LPS- or Con A-stimulated- thymocytes and splenocytes, and expression of CD69+CD4+ T cells in Con A-stimulated splenocytes were greatly increased in cells derived from pristane-induced lupus mice compared to normal mice. In addition, splenic T cells and CD4+ T cells in thymocytes from pristane-induced lupus mice were more resistant than nonautoimmune normal cells to Con A-induced apoptosis. Our findings indicate that immunoregulatory abnormalities of T cells and hyperreactivity of B cells in the in vitro immune responses in pristane-induced lupus mice may explain some of lupus pathogenesis.

Bamboo Culm Extract Downregulated Activation of NKT- and B- cells and Production of IL-6 in Pristane-Induced Lupus Mice

채병숙,Byung Hyun Park 한국생약학회 2009 Natural Product Sciences Vol.15 No.4

Lupus is characterized by immunoregulatory abnormalities between T- and B-cells leading to autoantibody production and multiorgan injuries. We investigated whether bamboo culm extract (BC) ameliorates aberrant activation of T cells and B cells and attenuate production of IL-6 in pristane-induced lupus mice. Lupus was induced by i.p. a single injection of 0.5 ml of pristane in female BALB/c mice, which, later about 4 months, were used as a lupus model. The pristane-induced lupus mice and healthy mice were injected i.p. with BC 5 µl/kg or PBS once a day for 3 weeks. These results demonstrated that BC significantly decreased levels of serum and BAL IL-6 and production of IL-6 by macrophages with/without LPS, and downregulated expression of NKT cell and CD86+ CD45R/B220+, but not CD80+CD45R/B220+ and CD69+CD4+ in the splenocytes in pristaneinduced lupus mice. Moreover, BC greatly increased Con A-stimulated production of IL-6, IL-10 and IFN-γ by splenocytes obtained from pristane-induced lupus mice. Therefore, our findings suggest that BC may ameliorate lupus pathogenesis in pristane-induced lupus mice via downregulation of aberrant activation of NKT cells and B cells and inhibition of production of IL-6.

Bamboo Culm Extract Attenuates Early Development of Systemic Inflammation in Pristane-Primed Lupus Mice

채병숙 한국생약학회 2010 Natural Product Sciences Vol.16 No.4

Systemic lupus erythematosus (SLE) is characterized by systemic inflammation through production of inflammatory mediators and signaling abnormalities between T- and B- cells, leading to autoantibody production and multiorgan injuries. This study was investigated whether bamboo culm extract (BC) attenuates development of lupus systemic inflammation in the early stage in pristane-induced lupus mice. The pristane-induced lupus mice were administrated with BC 0.5 ml/kg or PBS and healthy mice with PBS orally once a day for 14 days. Our results showed that BC remarkably attenuated levels of serum TNF-a, IL-6, IL-10, IFN-g, PGE2, and VEGF, production of macrophages IL-6 and PGE2 and expression of macrophages IL-6 and COX-2 mRNA in the presence or absence of LPS in pristane-induced lupus mice. Also, BC remarkably reduced expression of CD40L on the splenic T cells and CD80 on the splenic B cells and upregulated the reduced apoptosis of splenic T cells and CD4+ T cells in pristane-induced lupus mice. Therefore, these findings suggest that BC may attenuate early development of lupus systemic inflammation via downregulation of inflammatory mediators and amelioration of abnormal signaling between T cells and B cells.

The Inhibitory Effect of Bamboo Culm Extract on the Development of Pulmonary Inflammation in Pristane-Induced Lupus Mice

채병숙,김대근,은재순,Gi Sung Kwon,신태용 한국생약학회 2010 Natural Product Sciences Vol.16 No.4

Pulmonary pathogenesis in lupus is characterized by interstitial inflammation and vasculitis in lungs. We investigated whether bamboo culm extract (BC) attenuates pulmonary inflammation and lung injury in pristane-induced lupus mice. The pristane-induced lupus mice and healthy mice were administrated with BC 0.5 ml/kg or PBS orally once a day for 14 days. Our results demonstrated that BC significantly attenuated levels of bronchoalveolar lavage (BAL) IL-6, IL-10, IFN-g, PGE2 and VEGF, and pulmonary vascular permeability in pristane-induced lupus mice. Therefore, these findings suggest that BC may inhibit development of pulmonary inflammation and lung injury in lupus.

Regulatory Effect of Fresh Rehmanniae Radix Extract on the in Vitro Productionof Proinflammatory Cytokines in Pristane-Induced Lupus Mice

채병숙,Jae Heon Yang 한국생약학회 2007 Natural Product Sciences Vol.13 No.4

Rehmanniae radix is known as a traditional medicine with anti-inflamatory and antioxidantactivities. However, whether Rehmanniae radix attenuates autoimmune inflammation in lupus models characterizedtolerance, and B cell hyperactivity remains unclear. We investigated the effect of fresh Rehmanniae radix methanolextracts (RGMeOH) on the in vitro overproduction of proinflammatory cytokines by immune cells from pristane-induced lupus BALB/c mice. These results showed that RGMeOH remarkably attenuated Con A-increasedoverproduction of proinflamatory cytokines, such as IL-2, IFN-γ, IL-6 and IL-10 by splenocytes from pristane-induced lupus mice. RGMeOH greatly reduced LPS-induced production of TNF-α by splenic macrophages fromby splenic macrophages and splenocytes. These findings suggest that RGMeOH may ameliorate lupus systemicinflammatory autoimmunity via down-regulation of TNF-α and T cell-dependent cytokine production.Keywordsfresh Rehmanniae radix, TNF-α, IL-6, IL-10, IL-2, IFN-γ, pristane, lupus

Regulatory Effect of Scutellariae Radix on the Proinflammatory CytokineProduction and Abnormal T-Cell Activation in Vitroin Pristane-Induced Lupus Mice

채병숙,신태용,오찬호,김대근,은재순,전훈,박정숙,Myoung Soon Kim,양재헌 한국생약학회 2007 Natural Product Sciences Vol.13 No.3

baicalensis is known as a herbal medicine with anti-inflamatory and anti-oxidativeactivities. However, effect of Scutelaria baicalensis on lupus pathogenesis that is characterized byimmune cels remains unclear. We investigated effects of Scutelariae radix methanol extract (SBMeOH) on theproduction of proinflamatory cytokines and abnormal activation of T cells in vitro in pristane-induced lupusBALB/c mice. These results demonstrated that SBMeOH significantly decreased the LPS-stimulatedproduction of TNF-α, IL-6, and IL-10 by splenic and peritoneal macrophages and IL-6 and IL-10 byoverproduction of IL-6, IL-10, and IFN-γ by splenocytes from pristane-induced lupus mice. Also, SBMeOHsignificantly atenuated the Con A-induced expresion of CD4+ T cels and CD69+CD4+ T cells but not CD8+T cells in pristane-induced lupus mice. Our findings indicate that SBMeOH may ameliorate lupus pathogenicinflammation and autoimunity via downregulation of proinflamatory cytokine production and abnormalactivation of T cells.KeywordsTNF-α, IL-6, IL-10, IFN-γ, CD4, CD8, CD69, lupus, pristane, Scutellariae radix

Hesperidin Improves the IL-6-Mediated Hepatic Insulin Resistance in Hepa-1c1c7 Cells

채병숙,김대근 한국생약학회 2012 Natural Product Sciences Vol.18 No.4

Hesperidin (HES) is a bioflavonoid with antioxidant, anti-inflammatory and anti-diabetic properties. IL-6 is well known as a primary proinflammatory cytokine that contributes to impaired insulin signaling in liver. This study was to investigate whether HES improves IL-6-mediated impairment of insulin sensitivity in liver. Hepa-1c1c7 cells were pre-treated with 50 and 100 mM HES in complete media for 1 h and then cultured in the presence or absence of IL-6 (20 ng/ml). These results demonstrated that HES restored IL-6-suppressed expression of IRS-1 protein, downregulated IL-6-increased expression of CRP and SOCS-3 mRNA, and inhibited LPS-induced production of IL-6 in Hepa-1c1c7 cells. These findings indicate that HES may ameliorate hepatic insulin resistance via improvement of IL-6-mediated impaired insulin signaling in hepatocytes.

Hesperidin Ameliorates TNF-a-Mediated Insulin Resistance in Differentiated 3T3-L1 Cells

채병숙,신태용 한국생약학회 2012 Natural Product Sciences Vol.18 No.4

Adipose inflammation is linked to the development of insulin resistance and type 2 diabetes. Hesperidin (HES) is a flavonoid with antioxidant, anti-inflammatory and anti-diabetic properties. However, whether HES improves inflammation-mediated insulin resistance in adipose tissues remains unclear. The purpose of this study was to investigate whether HES attenuates inflammation-mediated insulin resistance in adipose tissue. Herein, RAW 264.7 cells and differentiated 3T3-L1 adipocytes were pretreated with various concentrations of HES in complete media for 1 h and then cultured in the presence or absence of LPS or TNF-a. Our results demonstrated that HES remarkably inhibited LPS-induced production of IL-6, TNF-a, and NO by RAW 264.7 cells in a dose-dependent manner. Also, HES inhibited TNF-a-induced production of IL-6 and PGE2 in differentiated 3T3-L1 cells, while upregulated TNF-a-suppressed expression of adiponectin and PPAR-g mRNA. These findings suggest that HES may ameliorate inflammation-mediated insulin resistance in adipose tissue.

Prostaglandin E2-Mediated Dysregulation of Proinflammatory Cytokine Production in Pristane-Induced Lupus Mice

채병숙,신태용,김대근,은재순,임재윤,양재헌 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.4

Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE2 modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE2 in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE2 mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE2 and LPS-stimulated production of PGE2 by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 enhanced production of IL-6, IL-10, and NO but decreased TNF-α by macrophages and augmented IFN-γ, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 also enhanced production of IFN-γ, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE2 synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-α. Indo remarkably inhibited Con A-increased production of IFN-γ, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE2 may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-γ, and NO in pristane-induced lupus mice.

비장세포의 Th cytokine 생산에 있어서 chlorpyrifos의 영향

채병숙 한국환경독성학회 2002 환경독성보건학회지 Vol.17 No.4

A helper T (Th)1-mediated response is known to enhance cell-mediated immunity, while a Th2-mediated response is associated with the humoral immunity that is elevated IgE levels and eosinophitia. Prostaglandin (PG)E₂ results in the decreased capability of lymphocytes to produce Thl cytokines, with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T lymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX-PGE₂ pathway. The purpose of this study is to determine the effect of CPF on the in vitro production of Th cytokines and the role of PGE₂ on the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF (0. 1, 1, 10 and 100 μM) in the presence or absence of indomethacin or PGE₂ for 12 h and then were incubated with concanavatin (Con) A for 48 h. 'These results showed that CPF remarkedly reduced the production of splenie interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF significantly increased the Splenic IL-4 production at low doses (0.1 and 1 μm) but did not affect at high doses (10 and 100 μM). Indometbacin reduced the CPF-decreased production of IL-2 and IFN-γ in a dose-dependent manner and significantly attenuated the production of IL-4 increased by CPF 0.1 gM. High dose of CPF significantly reduced the PGE₂-decreased production of IL-2 and IFN-γ, while the PGE₂-induced production of IL-4 was significantly enhanced by CPF I p.M. These findings suggest that CPF may down-regulate the immune response of Thl type by the suppressed production of IL-2 and IFN-γ, with a shift toward a TO cytokine response. The CPF-decreased production of Th 1 cytokines may not he mediated by endogenous PGE₂. Also, CPF may attenuate the exogenous PGE₂-decreased Thl immune response in a dose-dependent manner but may affect dose-independently the PGE₂-induced Th2 immune response.