• 생약학회지
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• 제45권3호
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• pp.256-261
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• 2014

Bee venom (BV) therapy has been used as a traditional medicine to treat a variety of conditions, such as arthritis, back pain, cancerous tumors, and skin diseases. However, regulatory effects of BV on tumor necrosis factor (TNF)-${\alpha}$-induced HaCaT cell migration or anti-inflammatory have not been explored. In the present study, we investigated the effects of BV on HaCaT cell migration and anti-inflammation. HaCaT cell migration was evaluated by wound-healing assay. The pro-inflammatory cytokines such as TNF-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-8 were examined by ELISA or Western blotting. BV treatment led to an increase in migration of HaCaT cells for 24 and 48 h. Especially, 10 ng/ml of BV were significantly increased HaCaT cell migration. Also, BV suppressed the secretion of TNF-${\alpha}$, IL-$1{\beta}$, and IL-8 in culture medium with HaCaT cells. In addition, Western blot results demonstrate that BV suppressed the expression of TNF-${\alpha}$ and IL-$1{\beta}$, in HaCaT cells. Especially, 1 or 10 ng/ml of BV markedly decreased the expression of pro-inflammatory cytokines. These results demonstrate the potential of BV for the prevention of skin inflammation induced by TNF-${\alpha}$.

• Journal of Chest Surgery
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• 제32권11호
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• pp.971-977
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• 1999

Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.

• Journal of Korean Neurosurgical Society
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• 제57권2호
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• pp.73-76
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• 2015

Objective : Tumor necrosis factor alpha (TNF-${\alpha}$) have proven effects in pathogenesis of neuroinflammation after spinal cord injury (SCI). Current study is designed to evaluate the effects of an anti-TNF-${\alpha}$ agent, adalimumab, on spinal cord clip compression injury in rats. Methods : Thirty two male adult Wistar rats were divided into four groups (sham, trauma, infliximab, and adalimumab groups) and SCI was introduced using an aneurysm clip. Animals in treatment groups received 5 mg/kg subcutaneous adalimumab and infliximab right after the trauma. Malondialdehyde (MDA) levels were studied in traumatized spinal cord tissues 72 hours after the injury as a marker of lipid peroxidation. Results : Animals that received anti-TNF-${\alpha}$ agents are found to have significantly decreased MDA levels. MDA levels were significantly different between the trauma and infliximab groups (p<0.01) and trauma and adalimumab groups (p=0.022). There was no significant difference in neurological evaluation of the rats using Tarlov scale. Conclusion : These results suggest that, like infliximab, adalimumab has favorable effects on lipid peroxidation induced by spinal cord trauma in rats.

• 한국산학기술학회논문지
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• 제14권11호
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• pp.5778-5784
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• 2013

본 연구는 항주름 소재를 개발하기 위해서 목단피로부터 gallic acid (GA)를 분리하여 항산화능을 측정하였고, HaCaT 세포에서 세포독성을 측정하였다. 또한 HaCaT 세포에서 tumor necrosis factor alpha (TNF-${\alpha}$)에 의해 유도되는 matrix metalloproteinase-1 (MMP-1) mRNA 발현, protein 발현, 분비에 대한 GA의 영향을 관찰하였다. 결과로써 GA는 30 ${\mu}g/mL$의 $IC_{50}$과 함께 항산화능을 나타내었고, 그것의 항산화능은 합성항산화제인 butylated hydroxyanisol (BHA)보다 높았다. GA는 HaCaT 세포에서 고농도인 200 ${\mu}g/mL$ 처리시 약한 세포독성을 나타내었다. 또한 HaCaT세포에서 TNF-${\alpha}$ (10 ng/mL)의 처리에 의해 증가된 MMP-1의 mRNA 발현, protein 발현, 분비는 GA의 처리에 의해 농도 의존적으로 유의적인 감소를 나타내었다(p<0.05). 그러므로 GA는 항산화 효과와 TNF-${\alpha}$로부터 유도되는 MMP-1의 발현을 저해함으로써 피부 주름을 개선할 수 있는 주름개선제로서의 활용가능성을 확인하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제6권5호
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• pp.269-274
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• 2002

A large number of factors such as osteotropic hormones, cytokines, or growth factors are related to the bone remodeling which is characterized by the coupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Recent investigations have indicated that cytokines such as $interleukin-1{\beta}\;(IL-1{\beta})$ and tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ play a potential role in the bone resorption associated with a variety of pathological conditions such as inflammatory osteolytic disease. Collagen is the most abundant protein of the extracellular matrix of bone, and the participation of collagenase in bone resorption has been widely investigated. In this study, effects of $IL-1{\beta}$ and $TNF-{\alpha}$ on the release of collagenase from osteoblastic cells were measured. The gelatinase activity was also measured by gel substrate analysis (zymography) after electrophoresis of conditioned media of osteoblastic cell culture. $IL-1{\beta}$ increased the collagenase activity in ROS17/2.8 and HOS cell culture. $TNF-{\alpha}$ also increased the collagenase activity of osteoblastic cells. When two kinds of cytokines were treated simultaneously in the culture of osteoblastic cells, synergistic increase of collagenase activity was seen in ROS17/2.8 cells. $IL-1{\beta}$ and $TNF-{\alpha}$ significantly increased the collagenase activity after 6 hour treatment in the osteoblastic cell culture, and there was no additional increase according to the culture period. Osteoblastic cells released the gelatinase and molecular weight of this enzyme was measured about 70 KDa as assessed by zymogram. $IL-1{\beta}$ and $TNF-{\alpha}$ showed increase of the gelatinase activity produced by ROS17/2.8 and HOS cells. Taken together, this study suggested that $IL-1{\beta}$ and $TNF-{\alpha}$ can modulate bone metabolism, at least in part, by increased release of collagenase and gelatinase from osteoblasts.

• Journal of Microbiology
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• 제39권3호
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• pp.186-194
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• 2001

Scrub typhus, caused by Orientia tsutsugamushi infection, is clinically and histopathologically characterized by local as well as systemic inflammatory reactions, indicating that orientiae induce mechanisms that amplify the inflammatory response. To reveal underlying mechanisms of chemoattraction and activation of responding leukocytes, expression of chemokine and tumor necrosis factor alpha (TNF-$\alpha$) genes in murine peritoneal macrophages after infection with the obligate intracellular bacterium Ο.tsutsugamushi was investigated. The genes that were unregulated included macrophage inflammatory proteins l$\alpha$/$\beta$(MIP-l$\alpha$/$\beta$), MIP-2, monocyte chemoattractant protein 1(MCP-1), RANTES (regulated upon activation, normal T-cell expressed and secreted), gamma-interferon-inducible protein 10(IP-10) and TNF-$\alpha$. Peak expression of these chemokines and TNF-$\alpha$ was observed between 1 and 3 h after infection. These responses returned to or approached baseline preinfection levels 6 h after challenge. Semiquantitative reverse transcription (RT)-PCR analysis revealed dramatic Increases during infection in the steady-state levels of mRNA ceding for the inhibitory subunit of NF-kB (IkB$\alpha$), whose transcription is enhanced by binding of NF-kB within the IkB$\alpha$promoter region. Thus, Ο. tsutsugamushi appears to be a stung inducer of chemokines and TNF-$\alpha$ which may significantly contribute to inflammation and tissue damage observed in scrub typhus by attracting and activating phagocytic leukocytes.

• Tuberculosis and Respiratory Diseases
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• 제44권6호
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• pp.1271-1284
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• 1997

연구배경 : 종양괴사인자(tumor necrosis factor ; TNF)는 다양한 생물학적 기능을 가지고 있는 바, 그 중 생체 외에서 증명된 뚜렷한 항암 효과로 말미암아 최근 항암 유전자요법의 중요한 대상으로 관심을 모으고 있다. 현재 유전자 이입의 기술적 문제로 생체 외에서 암세포에 유전자 이입을 시행한 후 이를 다시 환자의 생체내로 이식하는 방법이 연구의 주종을 이루고 있다. 그러나 저자들의 과거의 연구를 포함한 여러 연구에서 TNF가 이입된 암세포는 TNF에 대해 내성을 보이는 것으로 증명되었고 이에는 새로이 방어 단백질을 합성하는 것이 관여할 것이라는 시사가 있었다. 이 획득내성의 기전을 밝히는 것이 종양생물학의 이해를 넓히고 보다 효과적인 항암 유전자요법을 개발하기위한 매우 중요한 과제로 생각된다.

• Clinical and Experimental Pediatrics
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• 제45권2호
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• pp.240-246
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• 2002

목 적 : 신사구체 질환의 발생과 진행에 있어서 tumornecrosis factor-${\alpha}$($TNF-{\alpha}$)의 혈청 농도가 관련이 있다는 것과 혈청 농도보다는 신장내 농도가 더 중요하다는 주장이 있다. 이에 본 연구자들은 신사구체 신염 질환인 HSP 신염(HSN)과 신증후군 질환인 특발성 신증후군(INS)에서 $TNF-{\alpha}$와 단백뇨와의 관련성을 알아보고자 했다. 방 법: 1998년 3월부터 2001년 3월까지 충북대학교병원 소아과를 방문한 HSP 21명, INS 22명을 대상으로 혈액과 소변을 채취하였다. 단백뇨가 있는 경우는 24시간 동안 단백량을 creatinine에 대한 비를 구하여 비교하였다. $TNF-{\alpha}$의 농도 측정은 mouse anti-human $TNF-{\alpha}$ 항체를 이용한 sandwitch ELISA법을 이용하였다. 통계는 Statistical Analysis System(SAS)을 이용하여 Kruskall-Wallis test, Wilcoxon rank sum test, Spearmann test, paired t-test를 시행하였으며 유의 수준은 P<0.05를 기준으로 하였다. 결 과 : HSP에서 신장 침범이 없는 환아보다 신장 침범을 보인 환아에서 $TNF-{\alpha}$ 농도는 혈청에서 높았으나(P=0.009) 요에서는 유의한 차이가 없었다(P=0.088). HSN에서 혈청 $TNF-{\alpha}$의 농도에 비례하여 요단백이 의미 있게 증가하였고(P=0.004), 요 $TNF-{\alpha}$의 농도에 따라 요단백이 증가하는 양상이었지만 통계적 의의는 없었다(P=0.053). INS에서 단백뇨와 관련하여 혈청에서 P=0.763, 요에서 P=0.007으로 요의 $TNF-{\alpha}$의 농도에서만 통계적 의의가 있었다. 결 론: HSN에서 혈청 $TNF-{\alpha}$의 농도에 비례하는 신사구체의 손상으로 인해 요단백이 증가하고, INS에서는 여과된 단백에 의한 신세뇨관의 손상과 이에 따른 요의 $TNF-{\alpha}$의 증가로 추론할 수 있다. 따라서 HSP 환아에서 초기에 혈청 $TNF-{\alpha}$의 농도를 낮추는 치료를 시행함으로서 신염으로 이환되는 것을 예방하고, HSN 환아에서도 혈청 $TNF-{\alpha}$의 농도를 낮추는 치료를 적극적으로 하여 병의 진행을 막을 수 있을 것으로 사료되며, 신증후군에서는 단백뇨를 줄이는 치료를 하여 신장의 병변이 악화되는 것을 지연시킬 수 있을 것으로 사료된다.

• 생명과학회지
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• 제18권9호
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• pp.1207-1211
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• 2008

Pro-inflammatory cytokine인 종양괴사인자-$\alpha$ (TNF-$\alpha$)는 B형 간염바이러스(HBV) 감염에 대한 면역반응의 중요한 매개인자이다. TNF-$\alpha$의 생산은 전사수준에서 주로 조절되며, TNF-$\alpha$ promoter 다형성은 TNF-$\alpha$ 유전자 발현을 변화시키기 때문에, TNF-$\alpha$ promoter 다형성이 만성 HBV 감염의 병태생리에 영향을 미칠 가능성이 높다. 그러므로, 본 연구에서는 TNF-$\alpha$ promoter 다형성과 만성 HBV 감염의 연관성을 조사하였다. 본 연구는 만성 HBV 감염환자 181명, HBV 감염이 자연적으로 치유된 201명, 그리고 건강한 대조군 170명을 대상으로 하였다. TNF-$\alpha$ promoter의 -308G/A와 -238G/A 다형성은 PCR-RFLP법을 통하여 분석하였다. 분석결과, 환자군에서 -308과 -238 유전자형의 분포는 자연치유군 및 건강대조군에서의 분포와 통계적인 차이를 보이지 않았다(p>0.05). 또한, 그룹 간에 allele frequency도 통계적 차이가 없었다(p>0.05). 따라서, 본 연구의 결과는 한국인에서 TNF-$\alpha$ -308과 -238 promoter 다형성은 만성 B형 간염 바이러스 감염의 발생과 연관성이 없음을 시사한다.

• 대한한의학회지
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• 제17권2호
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• pp.227-236
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• 1996

The effect of Ligustrum Lucidum(LL) on the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages were investigated. Stimulation of the cells with LL in the presence or absence of interferon-r(IFN-r) resulted in the increased accumulation of nitrite in the medium. To further examine the mechanism of LL induced. NO Synthesis, we evaluated the secretion of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ by LL in murine macrophages. Treatment of LL increased the secretion of bioactive $TNF-{\alpha}$ in cultured medium. In addition, LL induced NO production was decreased by the treatment of anti-murine $TNF-{\alpha}$. neutralizing antibodies, indicating that LL induced superoxide production was decreased by the treatment of anti-murine $TNF-{\alpha}$ neutralizing antibodies. These data suggested that LL induced superoxide production was related to $TNF-{\alpha}$ secretion. In conclusion, our results indicates that LL may enhance innate immune response and be applied as a immunoregulating drug improving phagocytosis.