• 생명과학회지
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• 제17권5호
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• pp.678-686
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• 2007

인간중간엽줄기세포는(Human mesenchymal stem cells, hMSC) 골수, 지방, 피부, 근육, 혈액에 존재하며, 뼈, 연골, 지방, 근육, 신경세포로 분화가능성이 보고되어 손상조직의 재생을 위한 재료로서뿐만 아니라 유전자치료의 매개체로 이용될 수 있는 가능성이 제안되고 있다. 인간중간엽줄기세포의 적절한 배양조건에는 소 태아혈청(fetal bovine serum, FBS)이 요구되어지므로 세포치료에는 소 태아혈청이 다수 포함되어 있을 것이며 세포배양 배지 유래 소 태아혈청의 단백질에 의한 면역거부반응이 우려된다. 이미 앞선 연구에서 자가혈청 하에서 인체지방줄기세포 분리와 계속적인 세포배양을 실시하였을 때 인체지방줄기세포의 증식능력과 다 분화 능이 유지되며 면역결핍 생쥐에 골수의 말초혈액에서 유래된 CD34세포 이식 시 안착 능을 촉진함을 보였다. 본 연구에서 인체지방줄기세포가 인체혈청 하에서 배양되었을 때 소 태아혈청 하에서 배양할 때 발현하는 표면항원을 유지함을 확인했으며 microarray를 사용하여 유전자 발현을 비교했다. 유 세포 분석을 통하여 인체혈청 하에서 계속적으로 배양된 인체유래지방줄기세포에서 HLA-DR, CD117, CD29 와 CD44 의 발현이 소 태아혈청 하에서 배양했을 때와 비슷함을 밝혔다. 그러나 인체혈청 하에서 배양된 인체지방줄기세포의 유전자 발현형태와 소 태아혈청 하에서 배양된 세포의 유전자 발현형태 간에는 상당한 차이를 보였다. 그러므로 본 연구는 인체혈청 하에서 배양된 인체지방기질줄기세포가 임상적용을 위한 선행 데이터로써 직접적인 추정을 하기 위해서는 인체지방기질줄기세포 이식연구에 in vivo 동물실험연구가 수행되어져야 함을 제시하고 있다.

• Journal of Ginseng Research
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• 제44권6호
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• pp.815-822
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• 2020

Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3⁺ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORgt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

• 동의생리병리학회지
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• 제21권1호
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• pp.209-213
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Salicis Radicis Cortex, A decoction has been mainly used for improvement of ozena and a diuretic effect in oriental medicine, but there was no study on the molecular mechanism of Salicis Radicis Cortex as an immunomodulator. Here we investigated the role of the aqueous extract of Salicis Radicis Cortex in the expression of inflammatory mediators, surface molecule, and related receptors in vitro and in vivo. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Salicis Radicis Cortex increased the production of secretary TNF-alpha and Nitric oxide, and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. Moreover, i.p. injection of water extract of Salicis Radicis Cortex significantly increased the secretion level of IFN-gamma and TNF-alpha, IL-2, IL-4 and IL-5 in serum of mice in vivo. Taken together, these results suggest that Salicis Radicis Cortex may regulate the immune response by secreting Th1 and Th2 types of cytokines in vivo and the possibility of its as natural immunostimulator.

• 동의생리병리학회지
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• 제24권2호
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• pp.290-295
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• 2010

Gamigunggui-tang (GMGGT) is one of the important prescriptions that has been used in oriental medicine. We investigated the inhibitory effect of an oral administration of hot water extract of GMGGT on the development of atopic dermatitis (AD) by using Balb/c mice. The induction of atopic dermatitis-like lesion was conducted by the removal of the back hairs and topical application of 2,4-Dinitrochlorobenzene (DNCB) on to the back skin repeatedly. GMGGT was orally administered at a different dose (10.0 mg/kg, 50.0 mg/kg). Skin reactions, consisting of increased ear thickness and the presence of ear inflammation, were observed in mice over three weeks. Oral administration of GMGGT significantly suppressed the skin lesions, ear swelling, spleen weight, total serum IgE in a concentration dependent manner, and also inhibited the infiltration of mast cells in the dorsal skin. In the present study, these results suggested that GMGGT extract inhibits inflammatory response atopic dermatitis. Therefore, GMGGT may be effective substances for the management of AD in human.

• 동의생리병리학회지
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• 제20권3호
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• pp.548-556
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• 2006

This study was to evaluate the effect of Samjayangchin-tang (STYCT) on mouse Th1 and Th2 cells' differentiation and ovalbumin (OVA)-induced allergic inflammation. The proliferation of mouse CD4 T cells and the secretion of Th1/Th2 cytokines under the influence of STYCT extract were measured as well as the amount of ${\beta}-hexosaminidase$ in RBL-2H3 cells and the levels of $TNF-{\alpha}$ and IL-6 secretion in Raw264.7 cells. BALB/c mice were orally administered with STYCT extract and simultaneously inoculated with OVA to induce allergic reaction and measure the level of total IgE, OVA-specific IgE and the production of IFN- g, IL-4, IL-5 by the spleen cells. When mouse CD4 T cell were stimulated with anti-CO3 and anti-CD28 for 48 hours in various concentrations of STYCT extract, it decreased proliferation of CD4 cells. CD4 T cells under Th1/Th2 polarizing conditions for 3 days with STYCT resulted in mild decrease of IFN- g in Th1 cells and significant decrease of IL-4 in Th2 cells. STYCT extract had a dose-dependent inhibitory effect on antigen-induced release of ${\beta}-hexosaminidase$ in RBL-2H3 cells. Treatment of STYCT extract on LPS stimulated Raw 264.7 cells showed dose-dependent decrease in IL-6 production. Oral administration of STYCT extract on OVA-induced allergic mice showed an inhibitory effect on the levels of total serum IgE and OVA-specific IgE by 53% and 44%, respectively. Culture of spleen cells with OVA resulted in significant increase of IFN- g by 54% and significant decrease of IL-4 and IL-5 by 42%, and 29%, respectively. The results show that STYCT does not strongly induce mouse T cells to transform into Th1 or Th2 but it has an anti-allergic effect in vitro, and that it also corrects the unbalance between the reactions of Th cells in allergic diseases.

• Food Science and Biotechnology
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• 제17권5호
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• pp.953-958
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• 2008

The object of this study was to investigate the immune-enhancing effects of Chlorella vulgaris (CV) on a deteriorated immune function by a protein-energy malnutrition (PEM) diet. Unicellular algae, CV were used as a biological response modifier. Male C57BL/6J mice were fed for 15 days with standard diet or a PEM diet, which is associated with decreased host immune defense. After 8 days, mice in the PEM diet group were orally administered by 0.05, 0.1, and 0.15 g/kg body weight of CV or distilled water. Nutritional parameters, and interferon (IFN)-$\gamma$ levels were significantly increased in the blood serum of the CV (0.15 g/kg)-treated group (29.6$\pm$2.8 pg/mL) compared to the non-treated PEM group (4.1$\pm$0.4 pg/mL, p<0.05). In addition, cell proliferation and production of cytokines were investigated via a CV (0.01, 0.1, and 1 mg/mL) treatment using a human T cell line MOLT-4 cell. The CV treatment (1 mg/mL) significantly increased the production of both IFN-$\gamma$ and interleukin (IL)-2 (51.3$\pm$3.4 and 285.9$\pm$18.8 pg/mL, respectively) compared to the control (51.3$\pm$3.4 and 442.6$\pm$14.3 pg/mL, respectively), but did not affect the production of IL-4. These results suggest that CV may be useful in improving the immune function.

• 한국식품영양과학회지
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• 제44권8호
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• pp.1121-1127
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• 2015

2,4-Dinitrochlorobenzene(DNCB) 유도 아토피 피부염 BALB/c 모델에서 외톨개 모자반 에탄올 추출물(MMEE)의 항아토피 효과를 알아보기 위해 육안평가, severity score, 혈청 내 total immunoglobulin E(IgE), interleukin(IL)-4, tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$), IL-10 분비량 및 비장 세포 배양액 내 IL-4, IL-5, IL-13, $interferon-{\gamma}$($IFN-{\gamma}$) 분비량을 측정하였다. DNCB 반복 도포로 아토피 피부염 증상인 건조, 홍반, 짓무름 등의 증상이 두드러지게 나타남을 확인하였고, 이러한 아토피 피부염의 증상은 MMEE의 처리로 인해 증상이 감소되는 것으로 나타났다. Severity score에서도 MMEE의 처리로 인해 DNCB 단독 처리군에 비해 점수가 낮아짐을 확인하였다. 혈청에서 total IgE 및 cytokine의 분비량을 측정한 결과 total IgE, $TNF-{\alpha}$, IL-4의 분비량은 DNCB 단독 처리군에서 증가하였으나 MMEE 처리구에서 normal 군과 유사한 수준으로 감소됨을 확인하였다. 반면 IL-10의 분비량은 DNCB 단독 처리군에서는 normal 군에 비해 감소하였으나 MMEE 처리구에서는 증가하였다. 비장세포 배양액 내에서 cytokine의 분비량을 측정한 결과 IL-4, IL-13 및 IL-5의 분비량은 DNCB 단독 처리군에서는 증가하였으나 MMEE 처리구에서는 normal 군과 유사한 수준으로 감소하였으며, $IFN-{\gamma}$의 분비량은 DNCB 단독 처리군에서는 감소하였으나 MMEE 처리구에서는 증가하여 정상군과 유의적인 차이를 보이지 않았다. 따라서 MMEE는 DNCB 유도 아토피 피부염 동물 모델에서 Th1/Th2 cytokine의 활성 조절 및 total IgE 분비 억제를 통해 아토피 피부염 증상 개선에 효과를 가지는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권6호
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• pp.661-670
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• 2018

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

• 동의생리병리학회지
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• 제23권3호
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• pp.554-561
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• 2009

Soyangin-Hyeongbangpaedok-san(SHBPDS) is a herbal formula used for the common cold or upper respiratory illness. In order to investigate the effect of SHBPDS, mice were orally administered with SHBPDS alcohol extract for 7 days followed by intravenous anti-CD3 injection. In addition, splenocytes and CD4 T cells were cultured with SHBPDS in response to anti-CD3 in vitro and cytokines and transcription factors were evaluated. In vivo treatment with SHBPDS significantly augmented the expressions of the percentage of CD4 T cells and CD 69, an indicator of early T cell activation. Serum levels of IL-4 were significantly increased but those of IFN-${\gamma}$ and IL-2 did not reach statistical significance. The expressions of IFN-${\gamma}$ and T-bet mRNA were significantly downregulated in SHBPDS treated mice while those of IL-4 and C-Maf were significantly upregulated. In vitro stimulation of splenocytes and CD4 T cells by SHBPDS resulted in a reduction in IFN-${\gamma}$ secretion and STAT4 activity. The IL-4 releases from both cells were slightly reduced, but STAT6 activity was rather increased. In conclusion, SHBPDS exerted an inhibition in the expression of IFN-${\gamma}$, T-bet and STAT4 while IL-4, C-Maf and STAT6 were increased. Further studies are required to examine its pharmacological effects using more appropriate animal experiments.

• 한국식품영양과학회지
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• 제43권4호
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• pp.477-484
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• 2014

본 연구에서는 일반생강과 법제생강의 대장염 염증에 대한 억제 효과와 법제의 가공 처리가 일반생강의 염증 억제 효과보다 우수한 지를 비교하였다. Balb/c 수컷 마우스에 2.5% DSS로 궤양성 대장염을 유도하고, 일반생강과 법제생강 추출물 500 mg/kg을 투여하여 대장염의 염증 억제 효과를 연구하였다. 일반생강과 법제생강은 70% 에탄올로 열수 추출 및 농축하여 실험에 사용하였다. 일반생강과 법제생강 추출물 투여군 모두 대장 길이의 축소와 체중 감소가 대조군보다 유의적으로 억제되었다(P<0.05). 일반생강과 법제생강 추출물 투여군의 대장 길이는 7.6 cm와 8.0 cm로 법제생강 추출물 투여군의 대장 길이가 일반생강 추출물 투여군보다 더 길었다. 대장의 조직학적 관찰에서 대장의 길이의 축소 정도가 증가함에 따라 대장조직 점막층의 선와부의 파괴도 증가되었다. 대장염 염증 초기에 증가하는 염증성 biomarker인 혈청에서의 IFN-${\gamma}$, IL-6, TNF-${\alpha}$ 및 IL-12의 농도는 일반생강 추출물 투여군보다 법제생강 추출물 투여군에서 유의적으로 더 감소하였고, 대장 조직에서의 이들 사이토카인의 유전자 발현도 같은 경향을 나타내었다(P<0.05). 대장염 조직에서의 염증성 인자인 iNOS, COX-2의 유전자 발현에서도 일반생강군보다 법제생강군의 유전자 발현이 더 유의적으로 감소되었다. 이상의 결과로 DSS로 대장염이 유도된 마우스에서 일반생강과 법제생강의 추출물은 항 염증성 효과를 나타내었고, 법제생강 추출물의 대장염 염증 억제 효과가 일반생강 추출물보다 더 우수하였으며, 이는 법제가공 처리에 의해서 일반생강의 대장염 염증 억제효과가 증가되었다고 사료된다.