• Title/Summary/Keyword: IL-1 ${\beta}$, IL-6, TNF-${\alpha}$

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The Effects of Proinflammatory Cytokines and TGF-beta, on The Fibroblast Proliferation (Proinflammatory Cytokines과 TGF-beta가 섬유모세포의 증식에 미치는 영향)

  • Kim, Chul;Park, Choon-Sik;Kim, Mi-Ho;Chang, Hun-Soo;Chung, Il-Yup;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yong-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.861-869
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    • 1998
  • Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

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Lipopolysaccharide-induced Synthesis of IL-1beta, IL-6, TNF-alpha and TGF-beta by Peripheral Blood Mononuclear Cells (내독소에 의한 말초혈액 단핵구의 IL-1beta, IL-6, TNF-alpha와 TGF-beta 생성에 관한 연구)

  • Jung, Sung-Hwan;Park, Choon-Sik;Kim, Mi-Ho;Kim, Eun-Young;Chang, Hun-Soo;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yang-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.846-860
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    • 1998
  • Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.

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Effect of Berberine on the Proinflammatory Cytokines Production in Mice (베르베린이 마우스 전염증성 사이토카인의 생성에 미치는 영향)

  • Chung, Su-Ryoung;Choi, Myung-Won;Park, In-Dal;Kim, Kwang-Hyuk
    • Journal of Life Science
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    • v.20 no.8
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    • pp.1276-1280
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    • 2010
  • Berberine has shown a number of beneficial effects, including anti-tumor, anti-inflammation, and vasodilatory effects. In this work we investigated the effects of berberine on the production of proinflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-6 in mice. The supernatants of cultured splenocytes exposed with berberine or berberine plus LPS were harvested to assay TNF-$\alpha$, IL-$1{\beta}$, and IL-6. The sera from the mice injected with berberine or berberine plus LPS were then isolated to assay these cytokines. The TNF-$\alpha$ production in mice splenocyte cultures exposed to berberine was inhibited compared to the PBS control. The sera from LPS plus berberine injected mice showed lower levels of TNF-$\alpha$ compared to those of LPS only injected mice. The IL-$1{\beta}$ production in mice splenocyte cultures exposed to berberine was inhibited at a high dose (3.0 ${\mu}g/ml$) compared to the PBS control. Also, the increase of IL-$1{\beta}$ by LPS exposure in splenocyte cultures was inhibited by a high dose of berberine. The IL-6 in splenocyte culture supernatants showed lower levels after berberine compared to the PBS control. Also, production of IL-6 after LPS exposure in splenocyte cultures was inhibited by a low dose of berberine (0.3 ${\mu}g/ml$). These findings suggest the probability that berberine down-regulates the production of proinflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-6.

The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-$\beta$ from Monocytes of Balb/C Mice (Balb/C mouse의 폐장대식세포에서 유리규산 자극에 의한 Proinflammatory Cytokine과 TGF-$\beta$의 생성 및 상관관계)

  • Ki, Shin-Young;Kim, Eun-Young;Kim, Mi-Ho;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.823-834
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    • 1998
  • Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

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Spontaneous and Stimulated Release of the TNF-$\alpha$, IL-1$\beta$, IL-6 and IL-8 of Alveolar Macrophages in the Patients with Pulmonary Tuberculosis (폐결핵 환자의 폐포 대식세포에서 TNF-$\alpha$, IL-1$\beta$, IL-6 및 IL-8의 분비에 관한 연구)

  • Cheon, Seon-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.942-952
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    • 1998
  • The aim of this study was to evaluate spontaneous and LPS stimulated proinflammatory cytokines and chemokine release of alveolar macrophages in the patients with pulmonary tuberculosis and healthy individuals, as a control. Alveolar macrophages recovered from bronchoalveolar lavage fluids were cultured with or without LPS 0.1, 1, or 10 ${\mu}g/ml$ for 24 and 48 hours in 37C, 5% CO2. TNF-$\alpha$, IL-1$\beta$, IL-6 and IL-8 amount were evaluated using ELISA kit from the supernatants. There were a significant increase in the spontaneous 24 hours release of TNF-$\alpha$ and IL-6 from the involved segments of tuberculosis patients compared with uninvolved segments and normal control There were also increasing trends of release of them after LPS stimulation in involved segments, but not significant. IL-1$\beta$ and IL-8 were not evaluated from the involved segments of tubeculosis and there were not significant differences of them between uninvolved segments of tuberculosis and normal control. It is concluded that cytokine release of alveolar macrophages in the pulmonary tuberculosis was markedly increased, and it was localized to the alveolar macrophages from the involved segments.

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Silica induced Expression of IL-1$\beta$, IL-6, TNF-$\beta$, TGF-$\alpha$, in the Experimental Murine Lung Fibrosis (유리규산에 의한 폐장내 IL-1$\beta$, IL-6, TNF-$\alpha$, TGF-$\beta$의 발현)

  • Ki, Shin-Young;Park, Sung-Woo;Lee, Myung-Ran;Kim, Eun-Young;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.835-845
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    • 1998
  • Background: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well known. Method: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistochemical stain at 1, 2, 7 day, 2, 4, 8, 12 week, respectively. We investigated the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ in lung tissue. Results: 1) The expression of IL-6 increased from 1 day after exposure to 8 weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1 $\beta$ was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF-$\alpha$ expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-$\beta$ was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. Conclusion: The results above suggests IL-6, TNF-$\alpha$ appear to be a early inflammatory response in silica induced lung fibrosis and TGF-$\beta$ play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF-$\alpha$ production will be a key role in modultion of silica-induced fibrosis.

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Expression of TNF-${\alpha}$ and IL-$1{\beta}$ in Splenic Dendritic Cells and Their Serum Levels in Mouse Sparganosis

  • Yang, Hyun-Jong
    • Parasites, Hosts and Diseases
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    • v.49 no.2
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    • pp.191-194
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    • 2011
  • Sparganosis is a tissue invading helminthiasis infecting intermediate hosts, including humans. Strong immune responses are expected to occur in early phases of infection. Thus, we investigated cytokine expressions in splenic dendritic cells and in sera after experimental infection of mice. In splenic dendritic cells, TNF-${\alpha}$ and IL-$1{\beta}$ expression peaked at week 1 and week 3 post -infection (PI), respectively, and also early phase (week 2 PI) depressed cytokine expression was noticed. Serum IL-$1{\beta}$ concentration increased significantly at week 2 PI and peaked at week 6 PI, and that of TNF-${\alpha}$ peaked at week 6 PI. These results showed that pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$, are chronologically regulated in mouse sparganosis.

Effect of Gamikyejakjimo-tang(jiāwèiguìsháozhīm-tāng) ethanol extract on Rheumatoid Arthritis factors (가미계작지모탕(加味桂芍知母湯) 주정 추출물이 류마티스 관절염 인자에 미치는 영향)

  • Sim, Boo-Yong;Bak, Ji-Won;Kim, Dong Hee
    • The Korea Journal of Herbology
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    • v.29 no.5
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    • pp.65-73
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    • 2014
  • Objectives : The purpose of this study is to prove the effect of Gamikyejakjimo-tang (ji$\bar{a}$w$\grave{e}$igu$\grave{i}$sh$\acute{a}$ozh$\bar{i}$m-t$\bar{a}$ng, GK) on rheumatoid arthritis. Methods : We checked viability and measured production of IL-$1{\beta}$, IL-6, IL-17, TNF-${\alpha}$ in RAW 264.7 cell after treat by GK. Then we measured rheumatoid arthritis index score of DBA/1 mice with rheumatoid arthritis induced by CIA after GK oral administration, checked IL-$1{\beta}$, IL-6, IL-17, TNF-${\alpha}$ and hs-CRP tests in serum. Also we were observed mRNA expression of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ in spleen by RT-PCR. Results : GK showed cell viability of 100% or higher in all concentration in RAW 264.7 cells. GK inhibited LPS-induced productions of rheumatoid arthritis mediators cytokine in RAW 264.7cells. GK treated group showed improvement from rheumatoid arthritis at decreased the index score. Also, GK treated group decreased level in serum of IL-1b, IL-6, IL-17, TNF-a and hs-CRP tests by 31%, 35%, 20%, 57% and 58% respectively. Finally, GK treated group showed decrease expression of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ mRNA in spleen by 46%, 51%, 25% and 42% respectively. Conclusions : In this study, in-vitro and in-vivo results observed rheumatoid arthritis factors cytokine of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ decrease in RAW 264.7 cells, serum, mRNA expression. Also, GK showed decrease of inflammation figure in hs-CRP tests depending on effect of rheumatoid arthritis. Thus, these results can used as a effective drug of GK for rheumatoid arthritis.

ACTIONS OF RECOMBINANT $INTERLEUKIN-1{\beta}$, TUMOR NECROSIS $FACTOR-{\alpha}$ AND INTERLEUKIN-6 ON BONE RESORPTION IN VITRO (RECOMBINANT $INTERLEUKIN-1{\beta}$, TUMOR NECROSIS $FACTOR-{\alpha}$ 및 INTERLEUKIN-6의 골흡수 유도 효과에 관한 연구)

  • Lee, Yong-Moo;Choi, Sang-Mook
    • Journal of Periodontal and Implant Science
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    • v.24 no.1
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    • pp.155-164
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    • 1994
  • 치조골흡수는 만성치주질환의 전형적인 증상이다. 골흡수에 작용하는 여러 요인들 중에서도, 특히 최근에 들어서 몇몇 cytokine들에 대한 관심이 높아지고 있는데, interleukin-1(IL-1), tumor necrosis factor(TNF) 및 interleukin-6(IL-6) 등이 치주질환의 진행과정에서 중요한 치조골흡수요인으로 제안되고 있다. 본 연구의 목적은 신생쥐의 골조직 배양실험을 통해서 recombinant human $interleukin-1{\beta}$ ($rHuIL-1{\beta}$), recombinant human tumor necrosis $factor-{\alpha}$($rHuTNF-{\alpha}$) 및 recombinant human interleukin-6(rHuIL-6) 의 골흡수 유도효과를 알아보고, cyclooxygenase 억제제인 indomethacin과 recombinant murine $interferon-{\gamma}$($rMurIFN-{\gamma}$)가 이들 cytokine의 골흡수 유도능력에 미치는 영향을 알아봄으로써 이들 cytokine의 작용기구에 대해서 알아보고자 하는데 있다. 생후 1-2일된 쥐에게 $1{\mu}Ci^{45}CaCl_2$를 피하주사하고 4일 후에 쥐를 희생시켜 $^{45}Ca$ 로 표지된 두개골을 얻어 24시간 전배양 후, 각 cytokine ($rHuIL-1{\beta}$, $rHuTNF-{\alpha}$ 및 rHuIL-6)과 cytokine 및 첨가약제 (indomethacin 및 $rMurIFN-{\gamma}$)가 함유된 배지로 교환하여 48시간 배양한다. 골흡수 유도효과는 두개골에서 48시간의 배양 중 유리되는 $^{45}Ca$의 방사능 정도로 평가하였다. 본 연구를 통해 다음과 같은 결과를 얻었다. 1. $rHuIL-1{\beta}$ ($10^{-12}-10^{-9}M$) 및 $rHuTNF-{\alpha}$ ($10^{-10}-10^{-8}M$)는 농도변화에 따르는 골흡수 유도효과를 보였으나 , rHuIL-6 ($10^{-10}-10^{-8}M$)는 유의할 만한 효과를 보이지 않았다. 2. Indomethacin ($10^{-6}M$)은 $rHuIL-1{\beta}$$rHuTNF-{\alpha}$의 골흡수 유도작용에 유의할 만한 억제효과를 나타내지 않았다. 3. $rMurIFN-{\gamma}$ (1000 U/ml) 은 $rHuIL-1{\beta}$$rHuTNF-{\alpha}$의 골흡수 유도작용에 유의한 억제효과를 나타내었다. 본연구를 통해 치주질환 환자의 치주조직에서 검출되는 $IL-1{\beta}$$TNF-{\alpha}$가 치조골 흡수에 중요한 역할을 할 것으로 생각된다.

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EFFECT OF INTERLEUKIM-10 ON THE BONE RESORPTION INDUCED BY INTERLEUKIN-1B (Interleukin-10 이 $interleukin-1{\beta}$로 유도되는 골흡수에 미치는 효과)

  • Yu, Yun-Jung;Kang, Yun-Sun;Lee, Syng-Ill
    • Journal of Periodontal and Implant Science
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    • v.24 no.2
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    • pp.321-339
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    • 1994
  • The cytokines released by osteoblasts induce bone resorption via the differentiation of osteoclast precursors. In this process, $interleukin-1{\beta}$($IL-1{\beta}$)-induced bone resorption is mediated by granulocyte macrophage-colony stimulation factor(GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor ${\alpha}$($TNF-{\alpha}$) released from osteoblasts. Since these cytokines (GM-CSF, IL-6, $TNF-{\alpha}$) are produced by not only osteoblasts but also monocytes, and interleukin-10(I1-10) inhibits the secretion of these cytokines from monocytes, it may be speculated that IL 10 could modulate the production of GM-CSF, IL-6, and $TNF-{\alpha}$ by osteoblasts, then control $IL-1{\beta}-induced$ bone resorption. Therefore, the aims of the present study were to examine the effects of IL-10 on bone resorption. The sixten or seventeen-day pregnant ICR mice were injected with $^{45}Ca$ and sacrificed one day after injection. Then fetal mouse calvaria prelabeled with $^{45}Ca$ were dissected out. In order to confirm the degree of bone resorption, mouse calvaria were treated with Lipopolysaccharide(LPS), $TNF-{\alpha}$, $IL-1{\alpha}$, IL-8, $IL-1{\beta}$, and $IL-1{\alpha}$, Then, IL-10 and $interferon-{\gamma}$ ($IFN-{\gamma}$) were added to calvarial medium, in an attempt to evaluate the effect of $IL-1{\beta}-induced$ bone resorption. In addition, osteoclasts formation in bone marrow cell cultures, and the concentration of IL-6, $TNF-{\alpha}$, and GM-CSF produced from mouse calvarial cells were investigated in response to $IL-1{\beta}$ alone and simultaneously adding f $IL-1{\beta}$ and IL-10. The degree of bone resorption was expressed as the ratio of $^{45}Ca$ release(the treated/the control). The osteoclasts in bone marrow cultures were indentified by tartrate resistant acid phosphatase(TRAP) stain and the concentration of the cytokines was quantified using enzyme linked immunosorbent method. As results of these studies, bone resorption was induced by LPS(1 ng/ml ; the ratio of $^{45}Ca$ release, $1.14{\pm}0.07$). Also $IL-1{\beta}$(1 ng/ml), $IL-1{\alpha}$(1 ng/ml), and $TNF-{\alpha}$(1 ng/ml) resulted in bone resorption(the rations of $^{45}Ca$ release, $1.61{\pm}0.26$, $1.77{\pm}0.03$, $1.20{\pm}0.15$ respectively), but IL-8 did not(the ratio of $^{45}Ca$ release, $0.93{\pm}0.21$). The ratios of $^{45}Ca$ release in response to IL-10(400 ng/ml) and $IFN-{\gamma}$(100 ng/ml) were $1.24{\pm}0.12$ and $1.08{\pm}0.04$ respectively, hence these cytokines inhibited $IL-1{\beta}$(1 ng/ml)-induced bone resorption(the ratio of $^{45}Ca$ release $1.65{\pm}0.24$). While $IL-1{\beta}$(1 ng/ml) increased the number of TRAP positive multinulcleated cells in bone marrow cultures($20{\pm}11$), simultaneously adding $IL-1{\beta}$(1 ng/ml) and IL-10(400 ng/ml) decreased the number of these cells($2{\pm}2$). Nevertheless, IL-10(400 ng/ml) did not affect the IL-6, GM-CSF, and $TNF-{\alpha}$ secretion from $IL-1{\beta}$(1 ng/ml)-activated mouse calvarial cells. From the above results, it may be suggested that IL-10 inhibites $IL-1{\beta}-induced$ osteoclast differntiation and bone resorption. However, the inhibitory effect of IL-10 on the osteoclast formation seems to be mediated not by the reduction of IL-6, GM-CSF, and $TNF-{\alpha}$ production, but by other mechanisms.

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