• Clinical and Experimental Pediatrics
• /
• 제53권4호
• /
• pp.481-487
• /
• 2010

목 적: 최근 여러 연구결과 천식을 포함한 알레르기질환의 발병에 소아 성장시기에 알레르겐이나 내독소(LPS)등과 같은 물질에 노출이 중요한 역할을 하는 것으로 제시되었다. 이에 연구자들은 출생 초기에 기도 점막을 통한 알레르겐과 내독소에의 노출이 성장한 후에 알레르기 기도염증과 과반응성의 발생에 미치는 효과를 생쥐 모델을 통하여 규명하고자 본 연구를 시행하였다. 방 법: 실험동물은 무균 상태의 생후 1주이내의 암컷 BALB/c 생쥐를 사용하였다. 실험동물들에게는 각각 신생생쥐시기에 생리식염수, 1% ovalbumin (OVA), $1.0{\mu}g$ LPS, $1.0{\mu}g$ LPS in 1% OVA를 각 비공을 통하여 투여하였다. 실험동물은 연구 시작 제 35일부터 10일간 5% OVA로 감작시켰으며 최종 기도 감작 10일 후부터 3일간 1% OVA로 기도 항원유발을 시행하였다. 최종 기도유발 48시간 후 체적검사(plethysmography)를 이용하여 비특이적 기도과반응성 검사(Methcholine challenge test)를 시행하였으며 검사 후 실험동물을 희생시켜 검체를 취하여 BAL액내 세포분획, 사이토카인, 혈청 면역글로불린을 측정하였다. 결 과: 1) 메타콜린에 의한 기도과반응성은 생후 초기에 OVA, LPS, OVA/LPS를 투여한 군에서 생리식염수를 투여한 군에 비해 통계적으로 유의하게 억제되었다. 2) OVA, LPS, OVA/LPS를 투여한 군에서 BAL 액내의 호산구수와 IL-4, IL-5가 유의하게 낮았다. 3) 혈청내 OVA 특이 IgE는 OVA, LPS, OVA/LPS 투여군에서 유의하게 감소되었다. 결 론: 본 연구 결과 신생생쥐 시기의 점막을 통한 항원, 내독소의 노출이 성숙한 후 항원에 의한 기도염증 및 과반응성의 발생을 억제하였으며 향후 이러한 효과의 작용기전에 대한 연구가 필요할 것으로 생각한다.

• Journal of Applied Biological Chemistry
• /
• 제63권3호
• /
• pp.211-219
• /
• 2020

Quercetin은 항산화 및 항염증 활성이 잘 알려져 있으나, 건선 피부염 조절에 대한 효능 연구는 거의 보고된 것이 없어, in vitro 건선 피부염 시험 모델인 TNF-α/IL-17A 유도 HaCaT 세포주를 이용해 quercetin에 의한 건선 피부염 개선 효과를 규명하였다. 먼저, TNF-α에 의해 활성화된 HaCaT 세포주에 quercetin을 처리한 결과, IL-1α, IL-1β, IL-6 등 염증성 사이토카인 발현이 TNF-α 처리군 대비 각각 49.1±7.14, 42.8±8.16, 34.5±2.52% 억제되었다. Th17세포 및 수지상세포 등 면역세포를 염증 반응 부위로 유인하는 케모카인 IL-8 및 CCL20의 mRNA 발현량 또한 TNF-α 처리군 대비 38.4±5.83, 52.9±4.59% 감소하였다. TNF-α 자극에 의해 건선피부에서 비특이적으로 증가되는 케라틴 단백질 KRT6A 및 KRT16 발현뿐만 아니라, IκBα 및 STAT3 단백질의 인산화 또한 quercetin에 의해 유의적으로 억제되었다. 또 다른 건선 유발 사이토카인으로 알려진 IL-17A로 HaCaT 세포주를 자극한 후 quercetin에 의한 영향을 관찰한 결과, IκBα mRNA 발현은 55.8±5.28% 감소하였고, STAT3 인산화는 36.3±6.81% 하향 조절되었다. 마지막으로 TNF-α/IL-17A를 동시 자극한 HaCaT 세포주에 quercetin을 처리한 결과, IL-1α, IL-1β, IL-6, TNF-α, CCL20 유전자 발현이 모두 억제되는 것을 확인하였다. 이를 통해 quercetin은 기존 항산화, 항염증 활성뿐만 아니라 건선 피부염 개선에 활성을 갖는 소재임을 확인할 수 있었다.

• 대한한의학회지
• /
• 제32권3호
• /
• pp.10-17
• /
• 2011

Objective: To evaluate the immune-stimulatory potential of extracts of Broussonetia kazinoki Siebold (BK) on specific cellular and humoral immune responses in ovalbumin (OVA)-immunized mice. Material and Methods: C57BL/6 mice were immunized intraperitoneally with OVA/alum ($100{\mu}g/200{\mu}g$) on days 1, 8, and 15. BK (100, 300 or 1000 mg/kg) was given to mice orally for 21 days (from day 1 to day 21). At day 22, OVA-, lipopolysaccharide (LPS)- and concanavalin A (Con A)-stimulated splenocyte proliferation and OVA-specific and total antibodies were measured in plasma. Further, the effects of BK on expression of cytokine mRNA in OVA-immunized mice splenocytes were evaluated by RT-PCR analysis. Results: BK significantly enhanced OVA-, LPS-, and Con A-induced splenocyte proliferation in OVA-immunized mice (p<0.01). BK also significantly enhanced total IgM and OVA-specific IgG1 levels in plasma compared with the OVA control group. Moreover, BK up-regulated significantly the expression of mRNA level of IL-2 and IFN-${\gamma}$ in splenocytes. Conclusions: BK has immune-stimulating activity in an OVA-immunized mouse model system, enhancing the Th1 immune response. BK showed no cytotoxicity in this system, suggesting that BK may be a safe and effective adjuvant in humans.

• Parasites, Hosts and Diseases
• /
• 제52권6호
• /
• pp.605-612
• /
• 2014

Toxoplasma gondii is an intracellular protozoan parasite that causes a Th1 cellular immunity. Our previous study showed that T. gondii lysate antigen (TLA) treatment in S180 tumor-bearing mice resulted in tumor reduction by suppressing CD31 expression, a marker of angiogenesis. In the present study, to investigate tumor suppressive effect of TLA under the absence of T lymphocytes, athymic nude mice were compared with euthymic mice in the anti-tumorigenic effect triggered by TLA in CT26 tumors. According to the results, intratumorally injected TLA reduced tumor growth and TIMP-1 level, a metastatic marker, in both euthymic and athymic mice. TLA treatment led to a sharp increase in IL-12 expression in serum cytokine profiling of athymic mice, and increased MyD88 signals in macrophages derived from the bone marrow, implying the activation of innate immunity. The selective induction of IL-12 by TLA treatment had an anti-tumorigenic effect.

• 한국식품영양학회지
• /
• 제26권3호
• /
• pp.375-382
• /
• 2013

The present study is designed to explore an anti-tumor activity on crude extracts of Oplopanax elatus. Water extractions of Oplopanax elatus were performed at $100^{\circ}C$(OeE-100). OeE-100 doses up to $62.5{\mu}g/m{\ell}$ had no cytotoxicity on the tumor cell lines in vitro. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma, the prophylactic intravenous ($4{\sim}100{\mu}g/mouse$) or oral (2 mg/mouse) administration of OeE-100 significantly inhibited tumor metastasis as compared with tumor controls. Peritoneal macrophages stimulated with OeE-100 produced various cytokines such as TNF-${\alpha}$, IL-6 and IL-12. In an analysis of NK-cell activities, i.v. administration of OeE-100 ($10{\sim}100{\mu}g/mouse$) significantly augmented the cytotoxicity to YAC-1 tumor cells. Vaccination of mice with boiling-treated tumor cells (BT-vaccine) in combination with OeE-100 ($100{\mu}g/mouse$) showed higher inhibitions in tumor metastasis when compared with the mice of BT-vaccine treatment. In addition, the splenocytes from OeE-100 admixed BT-vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-${\gamma}$. These results suggested that the OeE-100 stimulated immune system and was a good candidate adjuvant of anti-tumor immune responses.

• 대한본초학회지
• /
• 제28권1호
• /
• pp.65-71
• /
• 2013

Objectives : Asthma is a chronic, complex respiratory disease, caused by airway obstruction, airway eosinophilic inflammation(AEI), and airway hyperresponsiveness(AHR). This study was conducted to determine whether oral administration of crude water extracts of Pinellia ternate Breitenbach(PTB) has an antiasthmatic potential in the treatment of asthma in mice. Methods : Asthmatic AEI and AHR were induced by systemic sensitization to ovalbumin(OVA) by intratracheal instillation with 0.1 mg/mL suspension of diesel exhaust particles(DEP) once a week for 10 weeks in BALB/c mice. Crude PTB water extracts(50 mg/kg and 200 mg/kg) were orally administered 5 times a week for 10 weeks. Cyclosporin(10 mg/kg) was administrered the same manner as a positive control. Results : Long-term treatment with crude PTB water extracts suppressed the infiltration of inflammatory cells, including eosinophils, into airways from blood. It also reduced asthmatic AEI and AHR by attenuating the increase in the levels of cytokines such as interleukin(IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid(BALF), as well as the levels of histamine and OVA-specific IgE in blood. However, the effect of crude PTB water extracts(200 mg/kg) was not likely to be stronger than that of cyclosporin(10 mg/kg). Conclusion : These results suggest that crude PTB water extracts have inhibitory effects on AEI and AHR in a mouse model of asthma and may act as a potential Th2 cytokine antagonist, and have a therapeutic effect on allergic asthma.

• 대한한방소아과학회지
• /
• 제32권3호
• /
• pp.1-15
• /
• 2018

Objectives Alismatis Rhizoma has been known to suppress inflammation and allergic reaction. However, the cellular target of Alismatis Rhizoma and its mechanism of action remain unclear. This study was designed to examine the effect of Alismatis Rhizoma extract (ALC) on the RBL-2H3 mast cells in vitro and on the OVA/alum sensitized mice ex vivo. Methods In the study, RBL-2H3 mast cells were cultured in minimal essential medium (MEM) for 24 hours, and treated separately with cyclosporin A and varying doses of ALC, and then stimulated with Phorbol 12-myristate 13-acetate (PMA) (50 ng/ml) and Ionomycin ($0.5{\mu}M$). The levels of IL-13, IL-4 were measured by ELISA analysis. The mRNA levels of IL-4, IL-5, IL-6, IL-13, GM-CSF, $TNF-{\alpha}$ were analyzed with Real-time PCR. Also, manifestations of MAPKs transcription factors and $NF-{\kappa}B$ p65 translocation were analyzed by western blotting in vitro. Subsequently, for ex vivo experiment, we induced allergic inflammation on Balb/c mice by OVA/alum and administered ALC orally. And we measured serum OVA-specific IgE level and IL-4, IL-13 in the splenocyte culture supernatant by ELISA analysis. Results ALC was shown to suppress mRNA expression of IL-4, IL-5, IL-6, IL-13, GM-CSF, $TNF-{\alpha}$, and to inhibit the IL-13, IL-4 production. Also ALC reduced an activation of mast cells specific signal MAPKs transcription factors and $NF-{\kappa}B$ p65 from the western blot analysis in in vitro experiment. In ex vivo, ALC oral adminstration decreased the level of OVA-specific IgE in serum, and IL-4, IL-13 in the splenocyte culture supernatant. Conclusions ALC is shown to reduce inflammation and allergic response by suppressing Th2 cytokines through the regulation of transcription factors MAPKs and $NF-{\kappa}B$ p65 in mast cells. Administration of ALC suppressed OVA-specific IgE in ovalbumin allergy model through the inhibition of Th2 cytokine. In conclusion, ALC can be considered as an effective treatment for allergic diseases such as atopic dermatitis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권9호
• /
• pp.5225-5230
• /
• 2013

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

• Journal of Microbiology and Biotechnology
• /
• 제23권8호
• /
• pp.1159-1166
• /
• 2013

Orientia tsutsugamushi, a gram-negative bacterium, causes severe acute febrile illness in humans. Despite this danger, the route of infection, infectivity, and protective mechanisms of the host's immune response to O. tsutsugamushi are unclear. Dendritic cells (DCs) are one of the most important cell types in bridging the innate and adaptive immune responses. In this study, we observed that O. tsutsugamushi infects and replicates in monocyte-derived DCs (MODCs). During infection and replication, the expressions of the cytokines IL-12 and TNF-${\alpha}$, as well as the co-stimulatory molecules CD80, CD83, CD86, and CD40, were increased in MODCs. When O. tsutsugamushi-treated MODCs were co-cultured with autologous $CD4^+$ T cells, they enhanced production of IFN-${\gamma}$, a major Th1 cytokine. Collectively, our results show that O. tsutsugamushi can replicate in MODCs and can simultaneously induce MODC maturation and increase proinflammatory cytokine levels in MODCs that subsequently activate $CD4^+$ T cells.

• Journal of Nutrition and Health
• /
• 제37권6호
• /
• pp.431-439
• /
• 2004

Scutellariae Radix (Scu.), one of the immune-regulatory substances, is recognized to play the role in the metabolic process of inflammation, allergy and immunity. It has been traditionally used in the Oriental medicine to treat inflammatory bowel diseases (IBD). The purpose of this study was to evaluate the effects of water extracts of Scutellariae Radix on the spleen lymphocyte immune function in the Balb/c female mice treated with dextran sodium sulfate (DSS) to induce colitis. Water extract of Scutellariae Radix (100 mg/kg) and sulfasalazine (50 mg/kg) were administrated orally for 2 weeks of experimental period. Mice were divided into three experimental groups randomly: DSS group (5％ DSS was ad libitum for 5 days) as control group, DSS ＋ Scu. (water extracts of Scutellariae Radix for 2 weeks after 5％ DSS was ad libitum for 5 days) as experimental group, and DSS ＋ Sulfasalazine group (Sulfasalazine for 2 weeks after 5％ DSS was ad libitum for 5 days) as positive control group. Levels of Ig A, Ig E, CD4$^{＋}$, CD8$^{＋}$, TNF-$\alpha$ and other cytokines were measured. Treatment of DSS for 5 days induced bowel inflammation and the treatment with Scu. water exteract and sulfasalazine significantly recovered the damage. The length of intestine of DSS group was significantly shorter than that of other groups. The serum and fecal concentration of Ig A of SS ＋ Scu group was higher than those of DSS group. The contents of CD4$^{＋}$ T cells was higher in the DSS ＋ Scu. group than the other groups and CD8$^{＋}$ T cells was the lowest in DSS ＋ Sulfasalazine group. The Ig A level of cultured supernatant of spleen lymphocyte was the highest, while the Ig E level was the lowest in SS ＋ Scu group. The concentration of TNF-$\alpha$, cytokine secreted from the Th1 cell in the supernatant spleen lymphocyte, was the highest in the DSS group and the lowest in the DSS ＋ Scu. group. The concentration of IFN-${\gamma}$ and ll...-12 was lower in the DSS ＋ Scu. group than those of the other groups. The concentration of IL-4 in the supernatant of spleen lymphocyte was the lowest in the DSS ＋ Scu. group but IL-10 was not significantly different. Based on these findings, water extract of Scutellariae Radix exhibited the inhibitory effect via IL-4 production thereby inhibited the production of Ig E and strengthened immune system, and alleviated injury in DSS- induced colitis mice model.