• Toxicological Research
• /
• 제34권1호
• /
• pp.65-73
• /
• 2018

Pretreatment of low-dose lipopolysaccharide (LPS) induces a hyporesponsive state to subsequent secondary challenge with high-dose LPS in innate immune cells, whereas super-low-dose LPS results in augmented expression of pro-inflammatory cytokines. However, little is known about the difference between super-low-dose and low-dose LPS pretreatments on immune cell-mediated inflammatory and hepatic acute-phase responses to secondary LPS. In the present study, RAW 264.7 cells, EL4 cells, and Hepa-1c1c7 cells were pretreated with super-low-dose LPS (SL-LPS: 50 pg/mL) or low-dose LPS (L-LPS: 50 ng/mL) in fresh complete medium once a day for 2~3 days and then cultured in fresh complete medium for 24 hr or 48 hr in the presence or absence of LPS ($1{\sim}10{\mu}g/mL$) or concanavalin A (Con A). SL-LPS pretreatment strongly enhanced the LPS-induced production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, TNF-${\alpha}$/IL-10, prostaglandin E2 ($PGE_2$), and nitric oxide (NO) by RAW 264.7 cells compared to the control, whereas L-LPS increased IL-6 and NO production only. SL-LPS strongly augmented the Con A-induced ratios of interferon (IFN)-${\gamma}$/IL-10 in EL4 cells but decreased the LPS-induced ratios of IFN-${\gamma}$/IL-10 compared to the control, while L-LPS decreased the Con A- and LPS-induced ratios of IFN-${\gamma}$/IL-10. SL-LPS enhanced the LPS-induced production of IL-6 by Hepa1c1c-7 cells compared to the control, while L-LPS increased IL-6 but decreased IL-$1{\beta}$ and C reactive protein (CRP) levels. SL-LPS pretreatment strongly enhanced the LPS-induced production of TNF-${\alpha}$, IL-6, IL-10, $PGE_2$, and NO in RAW 264.7 cells, and the IL-6, IL-$1{\beta}$, and CRP levels in Hepa1c1c-7 cells, as well as the ratios of IFN-${\gamma}$/IL-10 in LPS- and Con A-stimulated EL4 cells compared to L-LPS. These findings suggest that pre-conditioning of SL-LPS may contribute to the mortality to secondary infection in sepsis rather than pre-conditioning of L-LPS.

• 대한한의학방제학회지
• /
• 제20권2호
• /
• pp.83-92
• /
• 2012

본 연구를 통해서, 한(寒) 처방의 대표 처방인 황련해독탕(黃連解毒湯)과 열(熱) 처방의 대표 처방인 건강부자탕(乾薑附子湯) 모두 항염 효능을 확인할 수 있었으나, 그 작용 기전에 있어 뚜렷한 차이를 나타내었다. 이러한 차이는 한의학의 기본 이론인 한열에 대한 개념에 대한 연구의 초석이 될 수 있기를 바라며, 각 개별 약물의 효능 및 다른 처방들과 다른 기전적 실험이 추가적으로 필요할 것을 보인다.

• 대한수의학회지
• /
• 제39권6호
• /
• pp.1119-1125
• /
• 1999

Since Robert Koch found tubercle bacilli in 1882, the studies on tubercle bacilli of human and animal had been carried out. Being old tuberculin(OT) introduced in 1890, the specificity of the diagnosis of tuberculosis has been improved by continual uses of heat concentrated synthetic medium(HCSM) and purified protein derivatives(PPD) tuberculin. Now, two types of tuberculin test are used worldwidly ; the single intradermal test(SIT) using bovine tuberculin and the single intradermal comparative tuberculin test(SICTT) using avian and bovine tuberculins. In the SICTT, each countries have used with different combination of both avian and bovine tuberculins' titers. However, this kinds of studies have not reported in Korea. Therefore, the studies on the combination of their tuberculins' titers were performed through intradermal test of guinea pigs sensitized with either Mycobacterium bovis or M avium and were examined in 10 cattles of SIT positive reactors. Also, IFN-${\gamma}$ assay, the latest diagnostic method of bovine tuberculosis, was experimentally applied to SIT positive reactors. For determining the optimal titers, sensitized guinea pigs with M bovis and M avium were intradermally injected avian and bovine tuberculin. In guinea pigs sensitized with M bovis, bovine tuberculin 50 T.U. showed significant difference from all tested concentrations of avian tuberculin(p < 0.05). In guinea pigs sensitized with M avium, there is significantly different between bovine tuberculin and avian tuberculin by 25 T.U.(p < 0.01). Therefore, optimal titers of bovine and avian PPD tuberculins' titers for the SICTT in Korea were 5,000 and 2,500 tuberculin units, respectively, and the swelling diffences between bovine and avian site in SIT positive reactors were above 3mm. Also, in IFN-${\gamma}$ assay, the 9 SIT positive reactors were showed all the positive reactions.

• Journal of Korean Medical Science
• /
• 제33권52호
• /
• pp.336.1-336.12
• /
• 2018

Background: We aimed to investigate mucosal immunity related to forkhead box P3 ($FOXP3^+$) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-$ROR{\gamma}t$ antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin $(IL)-1{\beta}$, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon $(IFN)-{\gamma}$, soluble CD40L, and tumor necrosis factor-${\alpha}$. Results: $FOXP3^+$ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. $ROR{\gamma}t^+$ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 ($9.6{\pm}1.5$ vs. $12.7{\pm}3.0$), IL-21 ($14.9{\pm}1.5$ vs. $26.4{\pm}9.1$), IL-33 ($14.3{\pm}0.9$ vs. $19.1{\pm}5.3$), and $IFN-{\gamma}$ ($15.2{\pm}5.9$ vs. $50.2{\pm}42.4$) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 ($119.1{\pm}79.6$ vs. $52.9{\pm}39.1$) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A ($64.2{\pm}17.2$ vs. $28.3{\pm}10.0$) and IL-22 ($37.5{\pm}8.8$ vs. $27.2{\pm}3.7$) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased $FOXP3^+$ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

• Radiation Oncology Journal
• /
• 제15권3호
• /
• pp.175-186
• /
• 1997

목적 : 방사선조사가 세포내재성 병원균인 Listeria monocytogenes (LM)의 감염에 미치는 영향과 함께 감염면역과 밀접한 관계가 있는 대식세포에서의 $TNF-\alpha$ 및 Nitric oxide (NO) 생산능의 변화와 비장세포에서의 $IFN-\gamma$ 및 IL-2생산능에 미치는 영향을 알아보고자 본 실험을 시행하였다. 대상 및 방법 : 실험동물로는 BALB/c 마우스를 사용하였으며 Co-60 원격치료기를 이용하여 방사선을 조사하였다. LM감염에 미치는 영향을 관찰하기 위해서 방사선조사 1일후 $10^5$의 LM균을 복강내에 주사하고 1일, 3일, 5일후에 비장조직에서 LM생균수를 측정하였다. 방사선조사가 마우스의 생체내에서와 시험관내에서의 $TNF-\alpha$의 생산능에 미치는 효과를 관찰하기 위해서 각각 LPS로 유도하여 L929/Actinomycin D assay에 의해 $TNF-\alpha$량을 측정하였다. $IFN-\gamma$의 생성능은 방사선조사후 비장을 적출하여 비장세포액을 제조하여 Concavalin A (Con-A)로 자극한 후 정량검사를 하였다. IL-2의 생성능은 $IFN-\gamma$실험에서와 같이 비장세포를 얻어서 Con-A로 자극하여 CTLL-2세포의 성장촉진능력을 관찰함으로써 판정하였다. 방사선조사가 복강내 대식세포에서 생산되는 NO에 미치는 영향도 관찰하였다. 결과 : 방사선 (300cGy)을 조사한 군에 LM을 감염시킨 1일후 비장으로부터 검출되는 생균수는 대조군에 비해 감소하였으나 감염 3일 5일후의 생균수는 대조군에 비하여 오히려 증가하였다. 시험관내 복강대식세포에 방사선 (100-850cGy)을 조사하면 1일후 생산되는 $TNF-\alpha$의 양은 대조군에 비하여 증가하였으나, 방사선조사 (100-600cGy) 5일후 수집된 복강대식세포에 의한 $TNF-\alpha$의 생산은 오히려 감소하였고. 방사선조사 (300cGy)후 LM감염시 5일후 유도된 생체내 $TNF-\alpha$의 생산도 대조군에 비해 감소하였다. 방사선 (300cGy)을 조사한 마우스로부터 적출한 비장세포로부터 생산되는 $IFN-\gamma$와 IL-2의 양은 대조군에 비해 감소하였다. NO의 양은 100cGy 및 300cGy조사시 대조군에 비해 증가하였으며 그 이상 조사량을 증가하면 점차 감소하였다. 결론 : 방사선조사후 세포내재성 병원균인 LM감염에 대한 초기 저항성의 증가와 감염중반이후의 저항성 감소는 대식세포에서의 초기 $TNF-\alpha$ 생산능 증가후 감소, 그리고 T림프구에서의 $IFN-\gamma$및 IL-2 생산능 감소와 관련이 있을 것으로 사료된다.

• 한국약용작물학회지
• /
• 제17권2호
• /
• pp.90-96
• /
• 2009

The objective of this study was to investigate the effect of crude ginseng total saponins (CGS) against airway inflammation (AI) and airway hyperresponsiveness (AH) induced by diesel exhaust particles (DEP) in mice. AI and AH were induced by the intratracheal instillation with 0.1 $mg/m{\ell}$ of DEP suspension once a week for 10 weeks combined with ovalbumin (OVA) sensitization. Mice were also treated orally with 75 $mg/m{\ell}$ of CGS, 5 days a week for 10 weeks. Oral CGS treatment decreased in the level of serum immunoglobulin (IgE) and histamine increased by DEP and OVA, and declined respiratory resistance. It also dropped an enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice, and an increased T helper type 2 cell derived cytokine levels such as of interleukin (IL)-4, IL-13 and IL-5 in the BALF. However, it did not influence T helper type 1 cytokine such as interferon-gamma in the BALF. These results indicate that CGS may alleviate allergen-related AI and AH in mice and may play an important role in the modulation of asthmatic inflammation.

• Journal of Evidence-Based Herbal Medicine
• /
• 제2권1호
• /
• pp.19-24
• /
• 2009

GD68 is newly developed herb complex prescription. The constituent herbs of GD68 were Massa Medicata Fermentata, Atractylodis Rhizoma Alba, Poria, Zingiberis Siccatum Rhizoma, Crataegi Fructus, Saccarum Granorum, Agastachis Herba, Taraxaci Herba, Perillae Herba, Scutellariae Radix, Astragali Radix, Ginseng Radix, Houttuyniae Herba and Halloysitum Rubrum. The aim of this study was to examine feed value of GD68 in duck. The weight gain of ducks fed with supplemental GD68 high compared to those of the control. The feed intake and mortality of ducks fed with supplemental GD68 low compared to those of the control. The moisture, crude lipid and calorie content of the ducks fed GD68 were decreased, but the crude protein content of the ducks fed GD68 was increased. And we investigated the effect of GD68 on the production of cytokines in human T-cell line, MOLT-4 cells. GD68 plus concanavalin A (Con A) increased the interferon-$\gamma$ and interleukin-2 production compared with Con A alone. These results indicate that the supplemental GD68 may improve the production, meat quality and immunity of ducks.

• Journal of Microbiology and Biotechnology
• /
• 제27권10호
• /
• pp.1892-1895
• /
• 2017

IK can downregulate interferon-gamma-induced major histocompatibility complex (MHC) class II expression through the MHC class II transactivator, which suggests that IK can inhibit the interactions between immune cells. We delivered adeno-associated virus serotype 2 (AAV2) encoding the genes for truncated IK (tIK) or green fluorescent protein (GFP) to DBA1/J mice via intravenous injection. Seven weeks after injection, collagen-induced arthritis was induced in the AAV2-treated mice. AAV2-tIK injection reduced the severity of arthritis and the percentage of pathogenic Th17 cells compared with AAV2-GFP injection. These results suggest a novel gene therapy strategy for treatment of inflammatory arthritis.

• 약학회지
• /
• 제43권2호
• /
• pp.198-207
• /
• 1999

The aim of the present investigation was to examine whether YH439, a hepatoprotective agent, exerts protective effect against hepatotoxicity and reduces the production of cytokines and NO in lipopolysaccharide (LPS)-primed rats with carbon tetrachloride ($CCl_4$). Administration of LPS following a single dose of CCl4 injection resulted in remarkable elevations of the serum $TNF{\alpha},{\;}IL-l{\beta$ and IL-6 level. The serum NO level was moderately elevated and severe liver damage was evidenced by increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities. YH439 decreased the levels of TNF, $IL-l{\beta}$, IL-6, ALT, SDH as well as NO in the serum elevated by CCl4+LPS in a dose-dependent manner. Inducible nitric oxide synthase (iNOS) level was decreased in the liver of rats treated with YH439. The increased iNOS activity induced by LPS and $interferon-{\gamma}$ was significantly decreased in RAW 264.7 cells by YH439 treatment. YH439 increased the GSH level decreased by $CCl_4+LPS$ and suppressed the ratio of GSSG/GSH. The reduction of hepatotoxicity by YH439 may associated with the decrease in the production of cytokines as well as suppression of iNOS protein in conjunction with an increase in the GSH level.

• Food Science and Biotechnology
• /
• 제17권5호
• /
• pp.947-952
• /
• 2008

The unripe fruit of Momordica charantia (MC) has been shown to possess antidiabetic activity. However, the mechanism of its antidiabetic action has not been fully understood. In this study, the effects of the aqueous ethanolic extract of MC (AEE-MC) were evaluated on the apoptosis in pancreatic $\beta$-cells treated with a combination of the cytokines, interleukin (IL)-$1{\beta}$, tumor necrosis factor (TNF)-$\alpha$, and interferon (IFN)-$\gamma$. In MIN6N8 cells, the inhibitory effect of AEE-MC was significantly observed at 2 to 50 ${\mu}g/mL$: a 26.2 to 55.6% decrease of cytoplasmic DNA fragments quantified by an immunoassay. The molecular mechanisms, by which AEE-MC inhibited $\beta$-cell apoptosis, appeared to involve the inhibition on the expression of p21, Bax, and Bad, the up-regulation of Bcl-2 and Bcl-$X_L$, and the inhibition on the cleavage of caspase-9, -7, and -3 and poly (ADP-ribose) polymerase. This study suggests that MC may inhibit cytokine-induced apoptosis in $\beta$-cells and, thus, may contribute via this action to the antidiabetic influence in diabetes.