• 대한본초학회지
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• 제20권2호
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• pp.35-42
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• 2005

Objective : This study was performed to investigate the effect of oral administration of Oldenlandiae Diffusae Herba (ODH) on eosinophil, immunoglobulin-E and interleukin-4 in the experimental asthma induced by ovalbumin. Methods : Asthma was induced to Balb/c mouse by i.p. injection and aerosol immunization with ovalbumin. It was observed the change of the eosinophil number in the BALF. And, it was observed the change of the concentrations of IL-4 in BALF and splenocyte, IgE in serum by ELISA. Results : 1. The number of eosinophil in BALF was significantly decreased in ODH group copared with control group. 2. Concentration of IL-4 in serum, BALF and splenocyte was significantly decreased in ODH group compared with control group, respectively. 3. Level of IgE in serum was significantly decreased in ODH group compared with control group. Conclusion : We found that the effect of ODH extract in asthma was implicated in reductions of IL-4 released from Th2 cell, and decreases of IgE from plasma cell. These findings suggest that ODH extract can produce anti-asthmatic effect, which may playa role in allergen-induced asthma therapy.

• IMMUNE NETWORK
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• 제24권3호
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• pp.21.1-21.16
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• 2024

IL-1, a pleiotropic cytokine with profound effects on various cell types, particularly immune cells, plays a pivotal role in immune responses. The proinflammatory nature of IL-1 necessitates stringent control mechanisms of IL-1-mediated signaling at multiple levels, encompassing transcriptional and translational regulation, precursor processing, as well as the involvement of a receptor accessory protein, a decoy receptor, and a receptor antagonist. In T-cell immunity, IL-1 signaling is crucial during both the priming and effector phases of immune reactions. The fine-tuning of IL-1 signaling hinges upon two distinct receptor types; the functional IL-1 receptor (IL-1R) 1 and the decoy IL-1R2, accompanied by ancillary molecules such as the IL-1R accessory protein (IL-1R3) and IL-1R antagonist. IL-1R1 signaling by IL-1β is critical for the differentiation, expansion, and survival of Th17 cells, essential for defense against extracellular bacteria or fungi, yet implicated in autoimmune disease pathogenesis. Recent investigations emphasize the physiological importance of IL-1R2 expression, particularly in its capacity to modulate IL-1-dependent responses within Tregs. The precise regulation of IL-1R signaling is indispensable for orchestrating appropriate immune responses, as unchecked IL-1 signaling has been implicated in inflammatory disorders, including Th17-mediated autoimmunity. This review provides a thorough exploration of the IL-1R signaling complex and its pivotal roles in immune regulation. Additionally, it highlights recent advancements elucidating the mechanisms governing the expression of IL-1R1 and IL-1R2, underscoring their contributions to fine-tuning IL-1 signaling. Finally, the review briefly touches upon therapeutic strategies targeting IL-1R signaling, with potential clinical applications.

• 대한한방부인과학회지
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• 제34권1호
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• pp.34-47
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• 2021

Objectives: This study was designed to examine anti-inflammatory effect and mechanism of Citri Reticulatae Viride Pericarpium water extract (CRE). Methods: Cell cytotoxicity was tested with RAW 264.7 cells. To investigate anti-inflammatory effect of CRE in lipopolysaccharide (LPS)-induced RAW 264.7 cell, we measured nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). In addition, mitrogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) were examined by western blotting in LPS-induced RAW 264.7 cell with treated CRE. Results: In cytotoxicity analysis, CRE does not affect cell cytotoxicity. As compared with the control group, the expression of NO, PGE2, TNF-α, IL-6 were significantly decreased, and IL-10 was significantly increased in LPS-induced RAW 264.7 cell with treated CRE. As a result of Western blotting, there was concentration-dependent inhibition of pp38, pERK in MAPK pathway and significant reduction of pp65 in the NF-κB pathway. Conclusions: CRE might have anti-inflammatory effect in LPS-induced macrophages by promoting the production of IL-10.

• 대한한의학회지
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• 제27권1호
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• pp.220-228
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• 2006

Objectives : Interleukin-1 (IL-1)${\beta}$ in articular chondrocytes regulates differentiation, apoptosis, and inflammatory responses. It is still controversial, So, we investigated IL- $1{\beta}$ induces chondrocytes dedifferentiation and death. Also, we studied the role of the mitogen-activated protein kinase (MAPK) subtypes on IL-$1{\beta}$-induced dedifferentiation and apoptosis. Methods : To evaluation of dedifferentiation by chemokines of chondrocytes, we assessed such as proteoglycan, collagen, MMP-3 and MMP-13 by RT-PCR analysis. Also, to assess of apoptosis effect by chemokines, we measured annexin V/propidium iodode (PI) and sub G1 cells in chondrocytes by flowcytometric analysis Results : IL-$1{\beta}$ treatment did not affect activation of ERK-1/2, but stimulation of p38 kinase. Inhibition of phospho ERK-1/2 with PD98059 enhanced IL-1b-induced dedifferentiation, and apoptosis up to 13.5%, whereas inhibition of phospho p38 kinase with SB203580 inhibited dedifferentiation, and apoptosis. Conclusions : Our results indicate that SB203580, p38 kinase inhibitor, inhibits IL-$1{\beta}$-induced dedifferentiation, and apoptosis by the inhibition of type II collagen expression and proteoglycan synthesis of rabbit articular chondrocytes.

• 한국자원식물학회지
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• 제22권5호
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• pp.431-437
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• 2009

in vivo 및 in vitro에서 마황의 항염증효과를 검토하기 위하여 마황추출물을 급여한 흰쥐에게 LPS shock로 급성기 염증반응을 유발시킨 후, 혈액 및 간장의 전염증성 cytokines들의 농도를 경시적으로 조사하였으며, 한편으로는 Raw 264.7 cell에 LPS shock를 가한 후, 마황추출물이 각종 전염증성 cytokines들의 생산량에 미치는 영향을 조사했다. in vivo 실험에서, 각 처리군 별 plasma IL-$1{\beta}$, IL-6, TNF-$\alpha$ 및 IL-10 농도의 경시적 변동은 전 처리군 모두가 LPS 처리 후, 2h째 급격하게 증가하여, 5h째에 최고치를 나타내었다. Plasma IL-$1{\beta}$, IL-6 및 TNF-$\alpha$의 농도는 LPS처리 후 5h째에서 마황 첨가군 모두가 대조군보다 낮은 값을 나타내었다. Plasma IL-10의 농도는 LPS처리 후, 2h째 및 5h째 모두 에서 마황추출물 첨가군 들이 대조군보다 높은 값을 나타내었다. Raw 264.7 macrophages를 이용한 in vitro 실험에서, IL-$1{\beta}$, IL-6 및 TNF-$\alpha$의 농도들은 대조군보다 마황처리 군들 모두가 낮은 값을 나타내었다. IL-10의 농도는 대조군보다 마황처리군들이 다소 높은 경향을 보였으나, 유의한 차이는 아니었다. 이상의 결과들을 종합해보면 마황에 내재하는 기능성 물질들이 염증반응을 완화하는 효과를 가지고 있음을 시사해 준다.

• Parasites, Hosts and Diseases
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• 제34권3호
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• pp.185-190
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• 1996

폐흡층(Paragonimus westermani) 감염시 일어나는 TH cytokin 반응을 알아보고자 마우스에 폐흡충 피낭유충을 감염시킨 후 비장세포를 Con A로 자극하여 TH1-specific cytokine인 $IFN-{\gamma}$와 TH2-specific cytokin인 IL-4의 생산량을 감염시기별로 효소표식 면역검사법으로 측정하였다. 폐흡충 감염 마우스의 비장세포에서 생산되는 IL-4는 감염 후 3일($410{\;}{\pm}{\;}60.9{\;}pg/ml$)에 최고치에 도달한 후 2주($343{\;}{\pm}{\;}59.0{\;}pg/ml$)까지 대조군에 비해 높게 유지되었으나 감염 후 4주에는 감소되기 시작하여 6주에는 대조군의 생산량과 비슷하였다. 한편 폐흡충 감염 마우스의 비장세포에서 생산되는 $IFN-{\gamma}$는 감염 후 1주($151{\;}{\pm}{\;}32.2{\;}pg/ml$)에만 대조군에 비해 높게 증가되었을 뿐 2주부터 감소되기 시작하여 감염 후 6주에는 전혀 측정되지 않아 오히려 대조군의 생산량보다도 적었다. 또한 폐흡충 감염 마우스의 혈청 내 IL-4의 양은 감염 후 4주부터 6주에 대조군에 비해 높게 증가되었으며 혈청내 $IFN-{\gamma}$의 양은 전 실험기간을 통해 측정되지 않았다. 이상의 결과를 종합할때 폐흡층 감염마우스에서는 $IFN-{\gamma}$보다는 IL-4가 증가되는 TH2 cytokine 반응이 주로 일어남을 알 수 있었다.

• Archives of Pharmacal Research
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• 제27권9호
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• pp.923-929
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• 2004

Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E$_2$ (PGE$_2$), tumor necrosis factor-a (TNF-$\alpha$) and interleukin-1$\beta$(IL-1$\beta$), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE$_2$ production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Cheli-donium majus.

• 대한약침학회지
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• 제13권3호
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• pp.63-71
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• 2010

Objectives: Gallic acid (GA) is the major component of tannin which could be easily founded in various natural materials such as green tea, red tea, grape juice, and Corni Fructus. The purpose of this study is to investigate the effect of Gallic acid (GA) on production of interleukin (IL) in mouse macrophage Raw 264.7 cells stimulated by lipopolysaccharide (LPS). Methods: Productions of interleukins were measured by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$ (multi-analyte profiling beads) technology. Firstly, cell culture supernatant was obtained after treatment with LPS and GA for 24 hour. Then, it was incubated with the antibody-conjugated beads for 30 minutes. And detection antibody was added and incubated for 30 minutes. And Strepavidin-conjugated Phycoerythrin (SAPE) was added. After incubation for 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System and concentration of interleukin was determined. Results: The results of the experiment are as follows. 1. GA significantly inhibited the production of IL-3, IL-10, IL-12p40, and IL-17 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 25, 50, 100, 200 uM (p<0.05). 2. GA significantly inhibited the production of IL-6 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 50, 100, 200 uM (p<0.05). 3. GA diminished the production of some cytokine such as IL-4, IL-5, and IL-13 in LPS-induced mouse macrophage RAW 264.7 cells. 4. GA did not show the inhibitory effect on the production of IL-$1{\alpha}$ and IL-9 in LPS-induced mouse macrophage RAW 264.7 cells. Conclusions: These results suggest that GA has anti-inflammatory activity related with its inhibitory effects on the production of interleukins such as IL-3, IL-10, IL-12p40, IL-17, and IL-6 in LPS-induced macrophages.

• Tuberculosis and Respiratory Diseases
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• 제54권1호
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• pp.104-113
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• 2003

연구배경 : Rhinovirus(RV)는 상기도 감염의 중요한 원인균으로, 성인에서 기관지천식의 급성악화의 주요 원인이다. RV에 의한 기도염증반응의 기전은 잘 알려져 있지 않지만 interleukin(IL)-1, IL-6, IL-8 및 RANTES 등의 사이토카인을 매개로 일어난다. 염증반응에 관여하는 사이토카인의 발현은 적어도 전사인자 NF-${\kappa}B$에 의존성이므로 이러한 가설을 검증하기 위해 인체기도상피세포에서 RV에 의한 IL-8의 분비양상과 NF-${\kappa}B$ 활성화 단계에서 차단 제로 이용되는 N-acetyl-L-cysteine(NAC), PDTC, 및 TPCK를 투여하여 IL-8의 차단정도를 연구하여 NF-${\kappa}B$의 역할을 규명하고자 하였다. 방법 : 인체 기관지상피세포(BEAS-2B)와 RV type 14(RV14)를 ATCC로부터 구입하여 RV14 스톡을 만들고 역가를 측정하였다. 자극이 없는 대조군(배지단독)과 RV14를 상피세포에 감염시킨 후(MOI=1.0) 각각에서 2, 4, 6, 12, 24, 48 시간에 배양 상층액(SN)을 얻었다. 또한 대조군, RV14 자극군, NAC, PDTC, 및 TPCK 처치와 함께 RV14 자극을 준 군에서 각각 배양 12시간에 배양 상층액을 수집했다. SN에서 효소면역측정법으로 IL-8의 농도를 측정하였다. 결과 : 1) 상피세포는 RV14 자극이 없는 상태에서 배양시간의 경과에 따라 약간의 IL-8의 생산이 있었다. 2) 상피세포에 RV14 감염 후 4시간에서부터 IL-8이 증가하여 배양 48시간까지 지속적으로 증가하였다. 3) NAC와 PDTC는 RV14에 의한 IL-8의 생산을 유의하게 감소시켰으나, TPCK는 RV에 의한 IL-8의 생산을 억제하였지만 통계학적으로 유의하지 않았다. 4) NAC와 PDTC는 RV에 의한 IL-8 생성을 용량 의존적으로 억제하였다. 결론 : 일부 항산화제가 RV에 의한 기도염증반응을 차단할 수 있는 가능성을 제시하며 추후 NF-${\kappa}B$ 활성화 경로의 차단 부위에 대한 연구가 필요할 것으로 생각한다.

• IMMUNE NETWORK
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• 제6권1호
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• pp.20-26
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• 2006

Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that is characterized by invasive synovial hyperplasia, leading to progressive joint destruction. Recent studies have described that RA is caused by virus, bacteria or outside material. Approximately 2 to 20% of RA cases arc reported to be associated with infected hepatitis C virus (HCV). However, the mechanisms underlying virus-induced RA are still unknown. Moreover, few molecular studies have addressed the inflammatory aspects of HCV-associated autoimmune RA. In this study, we aimed to determine whe ther or not another HCV core protein transactivates the IL-8 gene expression, prototypic chemokine, in synovial cell. Methods: To establish the HCV core expressing stable synovial cell line, pCI-neo-core, a plasmid encoding HCV core protein, were transfected to HIG-82 cell line that is an established cell line from rabbit periaricular soft tissue. We examined the morphological changes and cell cycle distribution of HIG-82 cells with expression of HCV core protein by inverted microscopy and flow cytometry analysis, respectively. Also, we determined the mRNA levels of Interleukin (IL)-6 and IL-8 related to the inflammation by RT-PCR and then analyzed regulation of IL-8 expression by the NF-${\kappa}B$ pathway. Results: Our study showed no significant differences in morphology and cell cycle between HIG-82 control cell line and HIG-82 expressing HCV core protein. However, expression of HCV core protein induces the IL-8 mRNA expression in HIG-82 core cells via activated NF-${\kappa}B$ pathway. Conclusion: These results suggest that HCV core protein can lead to enhanced IL-8 expression. Such a proinflammatory role may contribute to the etiologic pathogenesis in RA patients with HCV infection.