• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.185-189
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• 2010

The present study demonstrates the effect of fibrates, agonists of $PPAR{\alpha}$ on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-$1{\beta}$ (10 ng/ml), $IFNP{\gamma}$ (10 ng/ml), and TNF-$\alpha$ (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and $10\;{\mu}M$) reduced the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation, released IL-6 level was measured. $IFNP{\gamma}$ and IL-$1{\beta}$ cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in $IFNP{\gamma}$ and IL-$1{\beta}$-stimulated astrocytes. Taken together, these results clearly suggest that activation of $PPAR{\alpha}$ attenuates the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation through IL-6 independent pathway.

• 약학회지
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• 제52권1호
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• pp.73-78
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• 2008

Immune system can protect host attacking from a variety of microorganism and virus through innate and adaptive immunities. The innate immune system can be activated by recognition of conserved carbohydrates on the cell surface of pathogen resulting in protection, immunity regulation and inflammation. Immunostimulating and anti-tumor ${\beta}$-glucan, major cell wall component of many fungi, could be recognized as pathogen associated molecular pattern (PAMP) by C-type lectin such as pathogen recognition receptor (PRR) of host innate immunity cells. In spite of many studies of basidiomycetes ${\beta}$-glucan on immunostimulation, little is known about the precise mechanism as molecular-level. Among C-type lectins, dectin-1 was cloned and reported as a ${\beta}$-glucan receptor. In this report, we demonstrated induction of cytokine gene transcription by Ganoderma lucidum ${\beta}$-glucan in the absence or presence of lipopolysaccharide (LPS) by RT-PCR analysis. The expression of murine dectin-1 (MD-1) on RAW264.7 macrophage by RT-PCR showing both the full length, 757 bp $(MD-1{\alpha})$ and alternative spliced form, 620 bp $(MD-1{\beta})$. Both $MD-1{\alpha}$ and $MD-1{\beta}$ mRNAs were induced by ${\beta $-glucan both in the absence and presence of LPS. To explore expression of inflammatory cytokines by ${\beta}$-glucan, RAW264.7 cells were treated with ${\beta}$-glucan for 12 hours. As a result, the expressions of IL-1 IL-6, IL-l0 and $TNF-{\alpha}$ were increased by ${\beta}$-glucan treatment in a dose-dependent fashion. From these results, ${\beta}$-glucan induced transcriptions of dectin-1 and immune activating cytokine genes, indicating induction of immune allertness by expressing dectin-1 and secreting inflammatory cytokines.

• 한방재활의학과학회지
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• 제21권1호
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• pp.35-46
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• 2011

Objectives : The present study investigated inflammatory effect of Rheum undulatum L. in lipopolysaccharide-exposed rats and Raw 264.7 cells. Methods : Male rats weighting $185.39{\pm}8.21g$ fed basal diet for 1 week and 32 rats were divided into a control group and 3 experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1time/1day) for 6 weeks. And we fed basal diet and administered an extract of Rheum undulatum L.(100 mg/kg, 200 mg/kg, 300 mg/kg, 1time/1day) to each experimental group of rats. We measured the plasma concentration of $IL-1{\beta}$($interleukin-1{\beta}$), IL-6 and $TNF-{\alpha}$(tumor necrosis $factor-{\alpha}$), liver cytokines, Raw 264.7 macrophages cytokines. Results : The plasma concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ peaked at 5h(hour) after LPS(lipopolysaccharides) injection, and the values of the Rheum undulatum L. extract groups were lower than those of the control group. In the increment of these cytokines concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5h after LPS injection, and the values of the Rheum undulatum L. extract groups were higher than those of the control group. In the increment of this cytokine concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were higher than that of control group. Liver cytokines measurement was done at 5h after LPS injection. The concentration of liver $IL-1{\beta}$ and IL-6 in the Rheum undulatum L. groups was lower than that of the control group. The concentrations of liver $TNF-{\alpha}$, and IL-10 showed no significant differences among all the treatment groups. In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, these values showed a tendency to decrease in the Rheum undulatum L. groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, the values showed a tendency to increase in the Rheum undulatum L. groups. Conclusions : These results indicate that the Rheum undulatum L. extracts have an functional material for inflammatory activities.

• 생명과학회지
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• 제10권4호
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• pp.362-364
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• 2000

Opuntia ficus-indca(Op) extract has been claimed to have several therapeutic properties in oriental medicine including anti-inflammatory and anti-rheumatoid arthritis effects. Little is known of its effect on the activation of immune cells such as T cells and macrophages. To evaluate the functional effect of Op extract on immune cells, we examined whether Op extract stimulates the proliferation of T cells and the secretion of cytokines including IL-1 beta, IL-6 and tumor necrosis factor-alpha in THP-1 cell lines by RT-PCR. Op extract significantly enhanced the proliferation of T cell clone(D10S). Transcription of cytokines including IL-1 beta, IL-6, and TNF-alpha peaked 6 hrs after exposure to Op extract(100g/ml) in the THP-1 cell line and declined and declined thereafter. In an experiment to test the dose dependency of transcription of cytokines, transcription increased at a dose of 10 g/ml and the maximum expression was obtained at 100 g/ml, 6 hrs after exposure to Op extract. These findings suggest that Op extract is a potent stimulant of immune cells including T cells and macrophages, which acts by stimulating T cell proliferation and upregulating cytokines. These phenomena imply that some edible plants may be beneficial to living animals through the activation of immune functions.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.823-834
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• 1998

연구배경: 유리규산(silica) 자극에 의해 폐장내 대식세포에서 형성되는 proinflammatory cytokines인 IL-1$\beta$, IL-6, TNF-$\alpha$와 fibrogenic cytokine인 TGF-$\beta$, PDGF는 섬유화 과정에 매우 중요한 역할을 한다. 그러나 이러한 cytokine 의 역할과 상호관련성에 대해서는 아직 확실히 밝혀진 바없다. 본 연구는 Balb/C mouse의 폐장단구세포를 silica로 자극시 형성되는 IL-6, TNF-$\alpha$ 폐섬유화의 발생과 유지에 중요한 역할을 할 것으로 기대되는 TGF-$\beta$ 의 생성을 관찰하고 TGF-$\beta$의 생성에 proinflammatory cytokine이 미치는 영향에 대해서 알아보고자 하였다. 방 법: Balb/C 의 폐장대식세포를 silica로 자극한 후 IL-6, TNF-$\alpha$ TGF-$\beta$의 양을 bioassay로 측정하였고 mRNA의 발현을 in situ hybridization을 통해 관찰하였으며, 대식세포의 TGF-$\beta$ 생성에 대한 IL-1$\beta$, IL-6, TNF-$\alpha$의 영향을 알기 위하여 L-1, IL-6, TNF-$\alpha$에 대한 중화항체를 이용하여 대식세포의 TGF-$\beta$의 생성 억제 유, 무를 관찰하였다. 결 과: Silica로 대식세포자극시 TNF-$\alpha$는 초기 4 시간째 최고의 생성능을 보였으며, IL-6 는 silica 0.2 ${\mu}g/ml$의 농도에서 배양 8 시간째 생성능이 가장 높았고 배양 12 시간째는 다시 감소하였다가 24시간째 증가하는 biphasic한 소견을 보여 주었다. TGF-$\beta$는 silica의 양과 관계없이 배양 24시간째 자연생성능뿐 아니라, silica로 자극시에도 증가되었다. Silica와 TNF-$\alpha$ 50ng/ml을 함께 자극시 TGF-$\beta$의 생성은 현저히 증가되었으며, TNF-$\alpha$ 50 ng/ml과 IL-6 50 ng/ml으로 동시 자극시에는 TNF-$\alpha$에 의한 TGF-$\beta$의 형성이 증가하는 경향을 보였다. TNF-$\alpha$의 중화항체를 전처치 후 silica 자극시 TGF-$\beta$의 생성능을 억제시킴을 관찰할 수 있었다. Anti-IL-$\beta$, anti-IL-6, anti-TNF-$\alpha$ antibody 모두를 통시에 투여하였을 때도 silica에 의한 TGF-$\beta$의 생성능을 억제시킴을 관찰할 수 있었다. Silica 자극 후 대식세포의 in situ hybridization에서 TNF-$\alpha$ mRNA는 2시간째부터 발현되었고 IL-6 mRNA는 4 시간째부터 발현된 후 8 시간째 소실되었고 TGF-mRNA는 12 시간째 가장 강한 발현을 보였다. 결 론: Silica 자극에 의해 폐장대식세포는 자극 초기에는 TNF-$\alpha$가 가장먼저 형성되고 후기에 TGF-$\beta$가 형성되며 TNF-$\alpha$가 TGF-$\beta$ 형성에 중요한 역할을 할 것으로 사료되었다.

• 약학회지
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• 제47권5호
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• pp.311-318
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• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

• Clinical and Experimental Pediatrics
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• 제50권9호
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• pp.912-918
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• 2007

목 적 : 산모의 알레르기 질환 병력 유무와 초유와 모유 간에 차이가 있는지 살펴보고, 또한 이들의 모유수유 기간에 따른 자녀의 알레르기 질환 발생 유무의 차이를 보고, 생후 2세까지 발생한 알레르기 질환과 모유 내의 면역학적 인자간의 연관성을 알아보고자 하였다. 방 법 : 2002년 5월부터 2003년 2월까지 참여를 희망한 총 138명의 산모에서 알레르기 질환이 있는 산모 88명과 알레르기 질환이 없는 산모 50명으로 나누어 조사하였다. 생후 2일경 초유와 생후 4주경의 모유를 채취하여, 초유와 모유 내 IL-4, IL- 6, IL-8, IL-10, IL-13, RANTES, $TGF-{\beta}1$과 $TGF-{\beta}2$를 측정하였다. 이후 소아는 생후 2세까지 알레르기 질환의 발생에 대한 추적관찰을 하였으며, 초유와 모유 내의 사이토카인과의 연관성을 비교하였다. 결 과 : 알레르기 질환이 있는 산모 군에서 6개월 이상 모유 수유하는 경우가 34.4%(n=21)였고, 3개월 미만으로 수유한 경우가 55.6%(n=15)로 두군 간에 통계학적 차이는 보이지 않았다(P>0.05). 초유 내의 IL-8 농도만이(P=0.021) 알레르기 질환이 있는 산모에서 더 높게 측정되었다. 반면 초유 내의 $TGF-{\beta}1$와 $TGF-{\beta}2$ 농도는 알레르기 질환이 없는 산모에서 더 높게 측정되었다(P=0.013, P=0.001). 초유나 모유 내 사이토카인과 생후 2세까지 알레르기 질환이 발생한 소아 간에 통계학적인 차이를 보이지 않았다. 결 론 : 생후 2세까지 발생한 알레르기 질환과의 연관성 있는 사이토카인은 발견하지는 못했다. 알레르기 질환이 있는 산모와 알레르기 질환이 없는 산모 간에 차이를 보인 $TGF-{\beta}1$, $TGF-{\beta}2$와 IL-8이 알레르기 질환의 병인에 연관성 조사를 위해, 추후 이들에서 장기간 추적 관찰이 필요할 것으로 생각된다.

• 한국식품위생안전성학회지
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• 제15권1호
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• pp.30-35
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• 2000

본 연구는 대장균 내독소로 실험적 패혈증을 유도한 토끼를 이용하여 지질성분과 cytokines에 대한 박테리아 내독소의 영향과 이 물질들 변화간의 상호 관련성을 조사한 결과이다. 내독소 투여군의 중성지방 및 콜레스테롤 농도는 전 검체채취 시간대에서 대조군보다 대체적으로 높았다(p<0.01 또는 0.05). 내독소 투여군의 인지질 농도는 내독소 투여후 3 및 6 시간대에 용량의존성으로 대조군보다 높았다(p<0.05). Tumor necrosis factor-$\alpha$ TNF-$\alpha$)와 interleukin-I$\beta$(IL-l$\beta$) 농도는 모든 검체채취 시기에서 대조군보다 증가하였다(p＜0.01 또는 0.05). 지질성분들의 변화와 cytokines(TNF-$\alpha$ 나 IL-1$\beta$)변화간에 유의한 음의 상관성이 있었으며(p<0.05), 중성지방이나 콜레스테롤 농도가 보다 높았던 내독소 투여 토끼들이 그렇지 않은 토끼들보다 상대적으로 더 좋은 임상상태를 보였다. 본 연구결과는 내독소에 의한 지질성분들의 변화가 지질 대사계의 혼란이라기보다 숙주 방어기작의 능동적 작용일 수도 있음을 시사하고 있다.

• 대한한의학회지
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• 제25권2호
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• pp.51-66
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• 2004

Objectives : To evaluate experimentally the clinical effect of Bojeongjeongcheon-tang, we observed the cytokines ($IL-1{\beta}$/TEX>, IL-4, IL-5, IL-6, IL-10, TNF-{\alpha},{\;}TGF-{\beta},{\;}IFN-{\gamma}$) and what effect they have on IgE in B cells of a rat. Methods : First of all, we extracted the spleens of healthy Balb/c mice and separated B cells from them. These B cells were cultured with anti-CD40 mAb (500 ng/ml), rmIL-4 (500 U/ml), Bojeongjeongcheon-tang (100 ug/ml, 10 ug/ml, 1 ug/ml). We used rmiL-10 (50 ng/ml) as a control group. Furthermore, we analyzed the expression of IgE, CD23, CD69 and the coherence of HRF in B cells using a flow cytometer. We also analyzed the cytokine gene expression in B cells by reverse transcriptase-PCR. We also measured B cells proliferation using the Liquid Scintillation Counter. Results : In this study, the Bojeongjeongcheon-tang treated group showed a tendency to decrease depending on the density compared with the control group in the expression of IgE+, CD23+, CD69, HRF. All of the Bojeongjeongcheon-tang treated group showed inhibitory effects with $IL-1{\beta}$, IL-4, IL-5 and proliferating effects with IL-6, IL-10, and $IFN-{\gamma}$ on cytokines transcript expression depending on the density. Meanwhile, $TNF-{\alpha}$ increased in all density. In IgE production, there was inhibitory effect on Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml) of significance (p < 0.01, p < 0.05). Also in B cell proliferation, the result revealed an inhibitory effect of Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml), of significance (p < 0.001, p < 0.01). Conclusions : This study shows that Bojeongjeongcheon-tang has an inhibitory effect on the production and activity of B cells. Also it inhibited CD23, IL-4 activity and IgE production and activation. It is obvious that Bojeongjeongcheon-tang treats asthma by inhibiting the production of histamine and HRF, IL-5 and proliferating IL-10. Also Bojeongjeongcheon-tang has some preventive effects on bronchial change by inhibiting $TGF-{\beta}$, which stimulates the bronchial transformation.

• 약학회지
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• 제45권6호
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• pp.715-723
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• 2001

Indomethacin is well known as a prostaglandin (PG) E$_2$ synthetase inhibitor which has antipyretic and anti-inflammatory 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 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)-$\alpha$ and interleukin (IL)-1$\beta$, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1$\beta$, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and interferon (IFN)-${\gamma}$ levels in supernatants, whereas indomethacin did not affect the LPS-increased levels of IL-2 and IFN-${\gamma}$. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1$\beta$, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-increased production of IL- 2 and IFN-${\gamma}$ in tumor-bearing state.