저용량 corticosterone로 전처리된 RAW 267.4 cells과 Hepa1c1c-7 cell에서 LPS로 유도된 염증성 매개인자들의 생산에 있어서 baicalin의 영향

채병숙(Byeong Suk Chae) 대한약학회 2022 약학회지 Vol.66 No.1

Low-dose glucocorticoids (GCs) are known to induce inflammation and immunosuppression. However, whether preconditioning with a low dose of GCs induces hepatic inflammation remains unclear. Although baicalin has beneficial therapeutic activity against liver damage, 100 μM baicalin enhances the lipopolysaccharide (LPS)-induced production of inflammatory acute-phase proteins in Hepa1c1c-7 cells. This study was performed to investigate the effect of 100 μM baicalin on the LPS-induced production of inflammatory mediators in liver cells, including Kupffer cells and hepatocytes, pre-conditioned with a low dose of GCs. RAW 267.4 cells and Hepa1c1c-7 cells were pretreated with 50 (cort 50) or 100 ng/mL (cort 100) corticosterone for 24 h and then cultured with 100 μM baicalin in fresh complete medium in the presence of LPS. Our results demonstrated that baicalin markedly decreased the LPS-induced production of TNF-α, IL-6, IL-1β, and nitric oxide in RAW 267.4 cells. Baicalin also strongly attenuated the LPS-induced production of TNF-α in cort 50- and cort 100-pretreated RAW 267.4 cells. Baicalin significantly upregulated the production of IL-6 induced by LPS and the production of VEGF decreased by LPS, but decreased the LPS-induced production of CRP in cort 100- pretreated Hepa1c1c-7 cells compared to untreated Hepa1c1c-7 cells. In conclusion, these findings suggest that 100 μM baicalin may enhance the LPS-induced production of inflammatory acute-phase proteins in hepatocytes, whereas it may downregulate these protein levels in macrophages and Kupffer cells. Moreover, preconditioning with a low dose of corticosterone may prime the effects of 100 μM baicalin on the LPS-induced production of IL-6 in hepatocytes, leading to hepatic insulin resistance or fatty liver disease.

RAW 264.7 Cell에서 리포폴리사카라이드로 유도된 염증성 매개인자들의 생산에 있어서 Corticosterone 전처리 효과

채병숙(Byeong Suk Chae) 大韓藥學會 2015 약학회지 Vol.59 No.5

Glucocorticoids are known to have anti-inflammatory effect. To investigate whether corticosterone pre-treatment enhances or not lipopolysaccharide (LPS)-induced production of inflammatory mediators, RAW 264.7 cells were pretreated with various concentrations of corticosterone for 24 h and then cultured without corticosterone in the presence or absence of LPS. Our results demonstrated that LPS remarkably increased production of TNF-α, IL-6, IL-1β, vascular endothelial growth factor (VEGF), and NO (nitric oxide). Corticosterone pretreatment significantly attenuated LPS-induced production of TNF-α, IL-1β, and VEGF, while significantly enhanced IL-6 and NO. These findings suggest that cor-ticosterone pretreatment may contribute to LPS-induced inflammatory responses in macrophages via pro- and anti-inflam-matory imbalance of inflammatory mediators.

프리스탄 유도한 루푸스 생쥐에서 사이토카인 Ex vivo 생산에 미치는 Baicalin의 효과

채병숙(Byeong Suk Chae) 大韓藥學會 2016 약학회지 Vol.60 No.1

Systemic lupus erythematosus (SLE) is characterized by dysregulatory production of proinflammatory cytokines and helper T (Th) cytokine-dependent autoantibody production. This study aims to investigate the protective effect of baicalin on the dysregulatory production of proinflammatory cytokines and Th cytokines in pristane-induced lupus mice. Mice were received i.p. a single injection of 0.5 ml of pristane, and then, later about 3 months, were used as a pristaneinduced lupus model. The pristane-induced lupus mice were administrated orally with baicalin 50 mg/kg once in a day for 10 days. Immune cells obtained from the pristane-primed lupus control group (lupus control) and baicalin-treated pristaneprimed lupus mouse group (BAC lupus) were cultured for 24 h or 36 h with/without mitogens. These results demonstrated that LPS-induced production of macrophage and splenic TNF-α and Con A-induced production of thymic IFN-γ were attenuated in BAC lupus compared to lupus control, while LPS-stimulated production of macrophage IL-10, Con A-stimulated production of splenic IL-10 and, PGE2-reduced production of splenic IFN-γ enhanced. Therefore, these findings suggest that baicalin may protect from autoimmunity and disease activity in lupus via modulatory effect of proinflammatory cytokine overproduction and Th cytokine imbalance.

리포포리사카라이드의 세포성 면역반응에 미치는 스와인소닌의 영향

채병숙(Byeong Suk Chae),안영근(Young Keun Ahn),김정훈(Joung Hoon Kim) 대한약학회 1998 약학회지 Vol.42 No.1

Effects of swainsonine (SW: 8alpha, beta-indolizidine-1alpha, 2alpha, 8beta-triol from Locoweed) on the cellular and nonspecific immune responses of lipopolysaccharide (LPS) were studied in ICR mice. Mice were divided into 4 groups (10mice/group), and LPS was given to each mouse 1 hr after i.p. injection with 3.7mg/kg of SW by i.p. injection twice a week for 14 days at a dose of 2mg/kg. Immune responses of the delayed-type hypersensitivity response (DTH) to sheep red blood cells (s-RBC), phagocytic activity and natural killer (NK) cell activity were evaluated. LPS treatment didn`t affect NK cell activity, phagocytic activity, DTH to s-RBC compared with those in controls, and phagocytic activity of sareoma 180 tumor bearing mice. However, circulating leukocytes were significantly decreased. Combinaton of LPS and SW increased circulating leukocytes significantly compared vath that in LPS alone, and DTH to s-RBC, NK cell activity and phagocytic activities of normal and sarcoma tumor bearing mice were not affected. These findings indicate that SW didn`t affected the cellular immune responses suppressed by LPS but significantly increased circulating leukocytes.

암유발생쥐에서 리포폴리사카라이드에 의해 유도된 사이토카인의 생산에 미치는 염화아연의 영향

채병숙(Byeong Suk Chae) 대한약학회 2001 약학회지 Vol.45 No.5

To determine effects of zinc on lipopolysaccharide (LPS)-induced production of proif1am-matory cytokines and Iymphokines in tumor-bearing ICR mice, this study has been investigated. Zinc chloride (Zn) at doses of 1 mghg was administered orally 30 minutes before I.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS greatly increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β, in both serum and splenic supernatants compared with those in controls. Howeverl Zn strongly decreased Lpsincreased production of TNF-α and IL-lβ in spleenic supernatants compared with those in controls and insignificantly also reduced in serum. LPS insignificantly decreased IL-2 levels in splenic supernatants compared with those in controls but significantly increased interferon (IFN)-γ. Levels. Zn didn't affect IL-2 production in splenic supernatants compared to controls but significantly enhanced the LPS- decreased production of IL-2. Zn significantly increased IFN-γlevels in splenic supernatants compared to controls and did not affect the LPS-increased production of IFN-γ. These findings suggest that Zn may strongly attenuate the LPS-induced pathogenesis of proinf1ammatory crtokines in tumor-bearing state and significantly up-regulate the LPS-induced function of T cells to produce IL-2 with maintaining normally the LPS-increased levels of IFN-γ.

과량의 아연에 노출된 생쥐의 사이토카인 생산에 미치는 인도메타신의 영향

채병숙(Byeong Suk Chae),신태용(Tae Yong Shin) 대한약학회 2002 약학회지 Vol.46 No.4

Zinc plays an important role in immunobiological responses, while excessive Binc attenuates immune aulctions in a dose-dependent manner Zinc excess has been reported to increase levels of plasma prostaglandin I s (PGE2), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inf1ammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE2 synthesis, on the proinf1ammatory cytosine and Iymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered I.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β Levels in both serum and splenic supernatants compared with those in ontrols, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1β. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-γ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-γ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-lβ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN- γbut not IL-2.

리포폴리사카라이드의 면역생물학적 반응에 미치는 염화아연의 영향

채병숙(Byeong Suk Chae) 대한약학회 1999 약학회지 Vol.43 No.1

Effects of zinc chloride (Zn) on the immune responses of lipopolysaccharide (LPS) were studied by using ICR mice. Mice were divided into 4 groups (10mice/group), and Zn was given to the mice with I.p. injection at 0.3mg/kg 5 times a week for 14 days, and 1hr after Zn administration, LPS was given with I.p. Injection at 5mg/kg twice a week. Mice were immunized and challenged with sheep red blood cells (SRBC). Immunobiological responses were evaluated by humoral, cellular and non-specific immunity. LPS treatment significantly increased the relative weights of spleen and thymus, hemagglutination titer (HA) and proliferation of splenocytes compared with those in controls, but significantly decreased the body weight gain. Zn treatment significantly increased proliferation of splenocytes and circulating leukocytes compared with those in controls. Combination of Zn and LPS significantly decreased the body weight gain and proliferation of splenocytes compared with those in controls. Combination of Zn and LPS significantly decreased HA and proliferation of splenocytes than in LPS alone. These finding indicate that zinc lowered the humoral immune responses of LPS.

Hepa1c1c-7 Cell에서 리포폴리사카라이드로 유도된 염증성 매개인자 생산에 있어서 코르티코스테론 전처리 효과

채병숙(Byeong Suk Chae) 대한약학회 2016 약학회지 Vol.60 No.1

Endotoxemia induces production of inflammatory mediators and acute phase proteins, leading to multiorgan injury and systemic inflammation. Hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoids (GCs) release modify endotoxemia-induced inflammatory responses. In the present study, we investigated whether pre-exposure of GCs influences endotoxin-induced production of inflammatory mediators in hepatocytes. Hepa1c1c-7 cells were pretreated with low concentrations of corticosterone for 24 h and then cultured without corticosterone in the presence or absence of LPS. Our results demonstrated that LPS alone significantly enhanced production of IL-6 and CRP but reduced vascular endothelial growth factor (VEGF) compared to controls. Combination of corticosterone pretreatment and LPS significantly upregulated production of IL-6, IL-1β, and VEGF but downregulated CRP compared to those in LPS alone. These findings suggest that in low concentration of corticosterone-preexposed hepatocytes, endotoxemia may induce upregulation of IL-6, IL-1β, VEGF and but downregulation of CRP.

암유발 생쥐에서 리포폴리사카라이드에 의해 유도된 사이토카인 생산에 미치는 인도메타신의 영향

채병숙(Byeong Suk Chae) 대한약학회 2001 약학회지 Vol.45 No.6

Indomethacin is well known as a prostaglandin (PG) E2 synthetase inhibitor which has antipyretic and anti-in1ammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin at the on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before I.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS remarkedly increased tumor necrosis factor (TNF)- α And interleukin (IL)- 1β, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1β, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and inter- feron (IFN)-γ levels in supernatants, whereas indomethacin did not affect the LPS- increased levels of IL-2 and IFN-. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1β, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-γincreasee production of IL-2 and IFN-γ in tumor -bearin g state.

사이토카인 생산에 미치는 생지황메탄올추출물의 효과

채병숙(Byeong Suk Chae),신태용(Tae Yong Shin) 대한약학회 2006 약학회지 Vol.50 No.3

We investigated the effect of fresh Rehmanniae radix methanol extracts (RGMeOH) in the in vitro production of cytokines by splenocytes and perigoneal macrophages isolated from C57BL/6 mice. Peritoneal macrophages and sple- nocytes were incubated with various concentrations of RGMeOH in the presence of 10μg/ml of lipopolysaccharide (LPS) or 1μg/ml of concanavalin A (Con A) for cytokine assay. These results showed that RGMeOH remarkably attenuated LPS-increased production of TNF-α but IL-6 by peritoneal macrophages and enhanced LPS-stimulated production of IL-10 in a dose-dependent manner. RGMeOH significantly augmented the LPS-or Con A-stimulated production of IL-2 and IFN-y by splenocytes. These findings suggest that RGMeOH may attenuate inflammatory responses through down-regulation of TNF-α and up-regulation of IL-10, and RGMeOH may up-regulate cell-mediated immune responses through increase in IL-2 and IFN-y production.