• Journal of Biomedical and Translational Research
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• 제19권4호
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• pp.92-102
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• 2018

The objectives of this study were to find out the plant to enhance immune activity among 42 kinds of foods frequently consumed by the Korean elderly consisting of 5 food groups and 5 wild plants. Each sample was assessed the immunoactive effect by measuring $NF-{\kappa}B/AP1$ gene expression, nitric oxide and cytokine production in $RAW-Blue^{TM}$ cell. Soybean sprouts of 47 plants showed the highest $NF-{\kappa}B/AP1$ gene expression at the level of $1.13{\pm}0.03$ (O.D. 650 nm) and Soritae, sweet potato, banana, apple, garlic, crown daisy, cabbage and Ailanthus altissima also had high activity of $NF-{\kappa}B/AP1$ gene in $RAW-Blue^{TM}$ cell stimulated by LPS. NO production of Ailanthus altissima was significantly higher than that of other plants and 16 plants of glutinous sorghum, black rice, Seoritae, Heuktae, sweet potato, banana, apple, garlic, mungbean sprouts, spinach, crown daisy, young pumpkin, cabbage, soybean sprouts, Actinidia arguta and Aster scaber were the next best activity. The above results selected 17 out of 47 plant samples. Moreover, soybean sprouts was significantly shown to increase $TNF-{\alpha}$ ($1,509.55{\pm}1.38pg/mL$) and $IL-1{\beta}$ ($54.56{\pm}1.08pg/mL$) cytokines in comparison with RAW-Blue cell stimulated by LPS. According to the results of in vitro evaluation, the ethanol extract of soybean sprout increased the production of immune-enhancing cytokines by proliferation of macrophages. In addition, $NF-{\kappa}B$ transcription factor activity and NO production ability were excellent, and it was selected as a material having excellent immunological activity.

• Nutrition Research and Practice
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• 제17권2호
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• pp.206-217
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• 2023

BACKGROUND/OBJECTIVES: The immunomodulatory effect of Platycodon grandiflorum (PG) has been reported, but studies on its mechanism are still lacking. This study was undertaken to confirm whether the hydrolyzed and fermented PG extract (HFPGE) obtained by adding hydrolysis and fermentation to the extraction process has an immune-enhancing effect in the in vivo system. MATERIALS/METHODS: Five-week-old BALB/c mice were divided into 4 groups: normal control group (NOR), control group (CON), 150 mg/kg body weight (BW)/day HFPGE-treated group (T150), and 300 mg/kg BW/day HFPGE-treated group (T300). The mice were administered HFPGE for 4 weeks and intraperitoneally injected with cyclophosphamide (CPA, 80 mg/kg BW/day) on day 6, 7, and 8, respectively, to induce immunosuppression. The levels of immunoglobulins (Igs) and cytokines were measured in the serum. In splenocytes, proliferation and cytokine levels were measured. RESULTS: Serum IgA, IgG, and IgM levels were observed to decrease after CPA treatment, which was recovered by HFPGE administration. The levels of serum interleukin (IL)-12, tumor necrosis factor (TNF)-α, IL-8, and transforming growth factor (TGF)-β were also decreased after exposure to CPA but increased after HFPGE administration. Decreased splenocyte proliferation was seen in CPA-treated mice, but was observed to increase in the T150 and T300 groups as compared to the NOR group. Compared to the CON group, splenocyte proliferation stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the HFPGE-treated groups was significantly increased. The cytokines secreted by ConA-stimulated splenocytes (IL-2, IL-12, interferon-γ, TNF-α) were increased in the T150 and T300 groups, and cytokines secreted by LPS-stimulated splenocytes (IL-4, IL-8, TGF-β) were also increased by HFPGE administration. CONCLUSION: These results suggest that HFPGE stimulates the immunity in immunosuppressed conditions, thereby enhancing the immune response. Therefore, it is expected that HFPGE has the potential to be used as functional food and medicine for immune recovery in various immunocompromised situations.

• 한국축산식품학회지
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• 제32권3호
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• pp.339-345
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• 2012

분만 후 3일 이내에 분비되는 임실 지역의 젖소 초유에서 유청 단백질을 효율적으로 분리하고 RAW 264.7 세포의 증식 및 면역활성에 미치는 영향을 조사하였다. 실험에 사용한 초유의 유청 단백질 g당 TGF-${\beta}1$은 875 pg/mL,TGF-${\beta}2$는 6,600 pg/mL이었으며 실험에 사용한 초유 유청 단백질 내 총 TGF-${\beta}$의 양은 7,475 pg/mL이었다. RAW264.7 세포에 대한 초유 유청 단백질 첨가에 따른 세포증식 정도를 알아본 결과 10 mg/mL의 농도까지는 세포성장을 유도하였으나 20 mg/mL 이상의 농도에서는 세포성장을 억제하였다. 이에 RAW 264.7 세포에서의 초유 유청 단백질의 면역관련 실험에 사용할 농도는 최대 10 mg/mL까지로 결정하였다. RAW 264.7 세포에 초유 유청 단백질(0-10 mg/mL)과 LPS(1 ${\mu}g/mL$)를 차례로 반응시키고 NO생성량을 측정한 결과 초유 유청 단백질이 농도 의존적으로 NO의 생성을 억제하였다. 또한 LPS 자극에 의한 염증성 사이토카인(TNF-${\alpha}$, IL-$1{\beta}$, IL-6)이 생성되는 과정에서 초유 유청 단백질의 효과를 확인하였다. 그 결과, LPS를 단독으로 첨가했을 때 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 농도가 모두 증가하였으나 초유 유청 단백질을 첨가한 경우에는 염증성 사이토카인의 생성이 농도 의존적으로 감소하는 경향을 보였다. 초유 유청 단백질에 의해 NO를 비롯한 염증성 사이토카인의 생성이 억제되는 것이 heme oxygenase-1의 발현과 관련하는지 알아보고자 초유 유청 단백질을 농도별(0-10 mg/mL)로 처리하여 heme oxygenase-1의 발현여부를 측정한 결과 대조군과 비교하여 3-4배 이상의 발현 증가를 보였다. 이상의 결과들로 미루어보아 LPS로 자극된 RAW 264.7 세포에서 TGF-${\beta}$ 등을 함유한 초유 유청 단백질은 10 mg/mL 이하의 농도에서 농도 의존적으로heme oxygenase-1의 발현을 유도하여 염증성 사이토카인인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6 및 NO의 생성을 억제하는 것으로 판단되었다.

• 생명과학회지
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• 제29권11호
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• pp.1251-1257
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• 2019

본 연구에서는 펩티도글리칸이 단핵세포의 $TNF-{\alpha}$ 발현에 미치는 영향을 조사하였고, 또한 펩티도글리칸에 의한 $TNF-{\alpha}$ 발현에 관련된 세포의 요소들을 연구하였다. 사람의 단핵세포주인 THP-1 세포를 펩티도글리칸에 노출시키는 경우 $TNF-{\alpha}$ 분비 증가뿐만 아니라 $TNF-{\alpha}$ 유전자 전사를 유도하는 결과를 가져왔다. TLR-2/4의 억제제인 OxPAPC은 펩티도글리칸에 의한 $TNF-{\alpha}$의 발현을 저해하였다. 그리고 U0126, SB202190, SP6001250, LY294002, Akti IV, rapamycin, NAC, DPI 같은 약리학적 저해제 또한 $TNF-{\alpha}$ 발현을 유전자/단백질 수준에서 상당히 약화시켰다. 그러나 polymyxin B는 $TNF-{\alpha}$ 발현에 영향을 주지않았다. 따라서 펩티도글리칸이 TLR-2, PI3K, Akt, mTOR, MAPKs, ROS 등을 통하여 단핵세포의 $TNF-{\alpha}$ 발현을 증가시킴을 확인하였다.

• IMMUNE NETWORK
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• 제11권6호
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• pp.364-367
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• 2011

Background: Prostaglandins (PGs) play pathogenic and protective roles in inflammatory diseases. The novel concept of PGs as immune modulators is being documented by several investigators. By establishing an in vitro experimental model containing human follicular dendritic cell-like cells, HK cells, we reported that HK cells produce prostaglandin $E_2$ ($PGE_2$) and prostaglandin $I_2$ ($PGI_2$) and that these PGs regulate biological functions of T and B cells. Methods: To investigate the respective contribution of cyclooxygenase-1 (COX-1) and COX-2 to $PGE_2$ and $PGI_2$ production in HK cells, we performed siRNA technology to knock down COX enzymes and examined the effect on PG production. Results: Both $PGE_2$ and $PGI_2$ productions were almost completely inhibited by the depletion of COX-2. In contrast, COX-1 knockdown did not significantly affect PG production induced by lipopolysaccharide (LPS). Conclusion: The current results suggest that mPGES-1 and PGIS are coupled with COX-2 but not with COX-1 in human follicular dendritic cell (FDC) and may help understand the potential effects of selective COX inhibitors on the humoral immunity.

• 대한한방부인과학회지
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• 제23권3호
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• pp.101-111
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• 2010

Purpose: To provide the information of efficacy for herbal formulas of high frequency, it was evaluated the anti-inflammatory effect. In many studies, plantderived anti-inflammatory efficacies have been investigated for their potential inhibitory effects on lipopolysaccharide (LPS)-stimulated macrophages. This study was performed to examine the anti-inflammatory effects of herbal formulas of high frequency on LPS-stimulated RAW 264.7 cells. Methods: Anti-inflammatory activity was investigated in 25 herbal formula extracts in vitro and in vivo. To investigate the anti-inflammatory effect in vitro model, using LPS-stimulated macrophages, RAW 264.7 cell line. The productions of nitric oxide(NO), prostaglandin(PG)$E_2$, interleukin(IL)-6 and tumor necrosis factor(TNF)-$\alpha$ were examined in RAW 264.7 cells, in the presence of the herbal formulas. RAW 264.7 cells were incubated with LPS $1\;{\mu}g/mL$ and herbal formulas for 18 hours. As an in vivo, using a rat model of carrageenin-induced paw edema. The paw volume was measured at 2 and 4 hours following carrageenin-induced paw edema in rats. Results: 8 kinds of herbal formula inhibited NO production by LPS-stimulated in some concentration, but the effect of NO inhibition is weak. 12 kinds of herbal formula inhibited $PGE_2$ production by LPS-stimulated over the 30%. Among them Gumiganghwal-tang, Sagunja-tang, Samchulkunbi-tang, Insampaedok-san and Hwangryunhaedok-tang inhibited IL-6 production by LPS-stimulated but TNF-$\alpha$ was not inhibited. 12 kinds of herbal formula reduced the carrageenin-induced paw edema in rats. Particularly, 3 kinds of herbal formula(Gumiganghwal-tang, Ssanghwa-tang and Soshiho-tang) were better than indomethacin. Conclusion: These results suggest that Gumiganghwal-tang, Sangunja-tang, Samchulkunbi-tang, Insampaedok-san and Hwangryunhaedok-tang have antiinflammatory activity.

• Tuberculosis and Respiratory Diseases
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• 제60권1호
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• pp.49-56
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• 2006

배경 : 급성 폐손상은 폐내, 외의 원인질환들에 의해 폐포-모세혈관의 투과성이 증가하며, 폐부종에 의해 급성 저산소성 호흡곤란이 유발되는 증후군이다. 헤파린은 항응고작용 외에 자체적으로 항염증효과를 가지고 있으나, 염증성질환에 헤파린을 투여하면 출혈성 합병증이 발생하기 때문에 실제로 임상에서 이용하는데 제약이 있다. 하지만 헤파린에서 2-O와 3-O sulfate를 제거하면, 항응고 효과가 제거되고 항염증효과는 지니고 있는 비항응고성 헤파린 (nonanticoagulant heparin)으로 변화한다. 본 연구에서는 흰쥐에게 내독소 (LPS)를 투여하거나, 출혈성 쇼크를 일으켜서 유발된 급성폐손상에서 비항응고성 헤파린의 치료효과를 살펴보았다. 방법 : 각 군당 5 마리 이상의 흰쥐 (Balb/c mouse)를 이용하였다. 미정맥 (tail vein)을 통해 생리식염수 또는 비항응고성 헤파린 (50 mg/kg)을 투여한 직후에 내독소를 복강으로 투여하거나 (1 mg/kg), 심장천자를 통해 총 혈액의 1/3 정도로 제거하여 출혈성 쇼크를 유도하여 급성폐손상을 유발하였다. 내독소 투여 또는 출혈성 쇼크 유발 1 시간 후에 흰쥐를 희생시키고 폐를 적출하였고, 폐의 염증성 변화는 사이토카인 ($TNF-{\alpha}$, MIP-2, $IL-1{\beta}$)을 측정하여 살펴보았고, 폐손상의 정도는 myeloperoxidase (MPO) assay와 wet-to-dry weight ratio를 측정하여 알아보았다. 결 과 : 내독소를 투여한 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현이 증가하고 ($TNF-{\alpha}$; $196.1{\pm}10.8$ vs $83.7{\pm}18.4pg/ml$, MIP-2; $3,000{\pm}725$ vs $187{\pm}26pg/ml$, $IL-1{\beta}$; $6,500{\pm}1167$ vs $266{\pm}25pg/ml$, p<0.05, respectively), 폐의 MPO 활성이 증가하였다 ($27.9{\pm}6.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 출혈성 쇼크를 일으킨 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현은 증가되지 않았으나, MPO 발현은 증가되었다 ($16.5{\pm}3.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 내독소 투여 또는 출혈성 쇼크에 의해 급성폐손상이 유발된 흰쥐에서 생리적 식염수를 투여하거나 비항응고성 헤파린을 투여한 군 사이에 사이토카인의 발현이나 MPO 활성에 의미있는 차이는 관찰되지 않았다. 결론 : 이상의 결과로 비항응고성 헤파린은 내독소를 투여하거나 출혈성 쇼크를 일으키고 한 시간 뒤에 측정한 흰쥐의 급성폐손상에서 의미있는 치료효과를 보이지 않았다.

• Nutrition Research and Practice
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• 제5권3호
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• pp.219-223
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• 2011

Obesity has been reported to be associated with low grade inflammatory status. In this study, we investigated the inflammatory response as well as associated signaling molecules in immune cells from diet-induced obese mice. Four-week-old C57BL mice were fed diets containing 5% fat (control) or 20% fat and 1% cholesterol (HFD) for 24 weeks. Splenocytes ($1{\times}10^7$ cells) were stimulated with $10\;{\mu}g/mL$ of lipopolysaccharide (LPS) for 6 or 24 hrs. Production of interleukin (IL)-$1{\beta}$, IL-6, and TNF-${\alpha}$ as well as protein expression levels of nucleotide-binding oligomerization domain (NOD)2, signal transducer and activator of transcription (STAT)3, and pSTAT3 were determined. Mice fed HFD gained significantly more body weight compared to mice fed control diet ($28.2{\pm}0.6$ g in HFD and $15.4{\pm}0.8$ g in control). After stimulation with LPS for 6 hrs, production of IL-$1{\beta}$ was significantly higher (P=0.001) and production of tumor necrosis factor (TNF)-${\alpha}$ tended to be higher (P < 0.064) in the HFD group. After 24 hrs of LPS stimulation, splenocytes from the HFD group produced significantly higher levels of IL-6 ($10.02{\pm}0.66$ ng/mL in HFD and $7.33{\pm}0.56$ ng/mL in control, P=0.005) and IL-$1{\beta}$ ($121.34{\pm}12.72$ pg/mL in HFD and $49.74{\pm}6.58$ pg/mL in control, P < 0.001). There were no significant differences in the expression levels of STAT3 and pSTAT3 between the HFD and the control groups. However, the expression level of NOD2 protein as determined by Western blot analysis was 60% higher in the HFD group compared with the control group. NOD2 contributes to the induction of inflammation by activation of nuclear factor ${\kappa}B$. These findings suggest that diet-induced obesity is associated with increased inflammatory response of immune cells, and higher expression of NOD2 may contribute to these changes.

• 대한한방내과학회지
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• 제29권1호
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• pp.12-24
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• 2008

Background and Objective : Chungsangboha-tang (CSBHT) has analgesic, sedative, anti-convulsive and anti-histamine effects, so it alleviates the symptoms of asthma. For the comparison of anti-inflammatory effect(s) on CSBHT, PD098059 was used as a negative control. Materials and Methods : This study emphasized THP-1 cells, which had been well characterized as a human monocytic leukemic cell line. The cells resemble monocytes with respect to several criteria and can be differentiated into macrophage-like cells by treatment with PMA. By using the MTS assay, it was possible to prove the safety of CSBHT. Results : Results shows that the CSBHT did not affected cell survival within $10^{1}$ ng/ml to $10^{5}$ ng/ml. Especially, $10^{5}$ ng/ml CSBHT treated cells show 70% deduction of $TNF-{\alpha}$ gene expression against that of LPS treated group. Furthermore, $IL-1{\beta}$, IL-6, IL-8, IL-10 and $TNF-{\alpha}$ levels are down-regulated when treated with CSBHT with concentrations up to 100 ug/ml on monocyte-derived macrophages. Interestingly, CSBHT-treated samples showed that overall transcriptional activities were down-regulated to 20% of that of PD098059 ($TNF-{\alpha}$ inhibitor). At protein level, the expression of $TNF-{\alpha}$ showed similar results as that of transcriptional activity. Results show that the protein level decreased more in the CSBHT-treated group (487 ${\pm}$ 87 pg/ml) than in the LPS-treated group (703 ${\pm}$ 103 pg/ml). In addition, the protein level of IL-8 in the CSBHT treated-group (9.84 ${\pm}$ 3.28 ng/ml) decreased similar as the expression of the control and PD098059-treated groups. Conclusion : CSBHT affects immune response, especially allergic responses and suppression of inflammatory reaction. The results provide us an alternative way to care for clinical inflammatory diseases, not only asthma but also the other possible general inflammatory and allergic diseases.

• Tuberculosis and Respiratory Diseases
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• 제53권5호
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• pp.519-529
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• 2002

연구배경 : 급성폐손상의 치료로 시도되는 표면활성물질의 효과는 허탈된 폐포를 재환기시키는 작용 외에 표면 활성물질 자제가 가지고 있는 항염증작용이 중요한 기전으로 생각되고 있다. 본 연구에서는 백서의 급성폐손상 모델을 이용하여 기관 내로 표면활성물질을 투여하였을 때, 기관지폐포세척액의 백혈구수와, 염증매개 사이토카인인 IL-$1{\beta}$ 그리고 IL-6의 농도에 변화가 있는지를 살펴보고, surfactant의 항염증작용이 전사인자인 NF-${\kappa}B$의 활성의 억제를 통하여 이루어지는지 여부를 Electrophoretic mobility shift assay (EMSA) 법으로 확인하였다. 방 법 : 대상동물은 300g 내외의 수컷 백서를 이용하였으며, 대상동물을 각각 6 마리씩 세 군으로 나누었다. 대조군은 기관 내로 생리식염수(3ml/kg)를 30분 간격으로 투여하였다. 나머지 두 군은 기관 내로 내독소(5mg/kg)를 투여하여 급성폐손상을 유발하고, 30 분 후에 표변활성 물질 치료군은 surfactant(30mg/kg)을 그리고 비치료군은 생리식염수(3ml/kg)을 각각 기관 내로 투여하였다. 생리식염수나 내독소를 투여한 24 시간 후에 기관지폐포세척술을 시행하였고, 기관지폐포세척액 내의 백혈구수와 IL-$1{\beta}$ 그리고 IL-6의 농도를 측정하였다. 또한 기관지폐포세척액에서 호중구를 분리하고 핵 단백질을 추출하여 NF-${\kappa}B$의 활성을 EMSA법으로 측정하였다. 결 과 : 대조군, 표면활성물질 치료군, 그리고 비치료군의 기관지폐포세척액의 백혈구 수는 각각 $356{\pm}275{\times}10^3/{\mu}1$, $3,221{\pm}1,914{\times}10^3/{\mu}1$, 그리고 $5,561{\pm}1,757{\times}10^3/{\mu}l$으로 비치료군의 백혈구 수가 가장 높았고, 다음으로 표면활성물질 치료군, 비치료군의 순서였다(p<0.05). 기관지폐포세척액의 IL-$1{\beta}$ 농도는 대조군은 0pg/ml, 표면활성물질 치료군은 $360{\pm}234pg/ml$, 그리고 비치료군은 $2,064{\pm}1,082pg/ml$로 대조군에 비해 표면활성물질 치료군이, 그리고 표면활성물질 치료군에 비해 비치료군의 IL-$1{\beta}$농도가 높았다(p<0.05). 기관지폐포세척액의 IL-6 농도는 대조군, 표면활성물질 치료군, 비치료군에서 각각 $49{\pm}62pg/ml$, $1,754{\pm}1,340pg/ml$, 그리고 $3,621{\pm}567pg/ml$으로 대조군에 비해 표면활성물질 치료군이, 그리고 표면활성물질 치료군에 비해 비치료군의 농도가 높았다(p<0.05). 표면활성물질 치료군과 비치료군 사이에서 호중구의 NF-${\kappa}B$ 활성화에는 차이가 없었다. 결 론 : 이상의 연구로 내독소의 기관 내 투여로 유발한 백서의 급성폐손상에서 기관 내로 투여한 표면활성물질은 기관지폐포세척액의 백혈구수와 염증매개 사이토카인인 IL-$1{\kappa}$ 그리고 IL-6의 농도를 감소시켜 폐포 내의 염증을 감소시켰으며, 표면활성 물질의 항염증작용은 NF-${\kappa}B$의 활성의 억제를 통하여 이루어지지는 않는 것으로 판단된다.