• Tuberculosis and Respiratory Diseases
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• 제42권3호
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• pp.302-313
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• 1995

연구배경: 종양괴사인자(Tumor necrosis factor; TNF)는 다양한 생물학적인 작용을 가지며 종양 세포에 대한 세포 독성은 그 대표적인 기능중의 하나이다. TNF-$\alpha$는 생체외에서(in vitro) 몇몇 종양 세포주에 대하여 항암제, 특히 topoisomerase II targeted chemotherapeutic agent의 세포 독성 효과를 상승적으로 증가시키는 것이 알려져 있다. 최근 암세포에 대한 cytokine 유전자 요법에서 TNF는 중요한 대상으로 여겨지고 있으며, 유전자 이입에 의해 암조직이 TNF를 생성하게 될 경우 암 증식 억제 효과가 있음이 보고되고 있다. 연구자는 암세포에 TNF-$\alpha$ 유전자를 이입하여 자신이 TNF-$\alpha$를 생성하도록 형질을 변환시킨 암세포는 topoisomerase II 억제 항암제에 대한 김수성에 변화가 있을 것이라는 가설을 수립하였고 이를 검증하고자 본 연구를 수행하였다. 본 연구에서는 생체외로(in vitro) TNF-$\alpha$ 유전자를 이입하여 TNF-$\alpha$를 생성하는 암세포주에서 topoisomerase II targeted drug에 대한 항암제 감수성 효과가 모세포주에 비하여 증대될 수 있는지를 알아 보고자하였다. 방법: TNF-$\alpha$에 감수성을 보이는 것으로 알려진 인체 중피종 세포주인 NCI-H2058 세포주 및 생쥐의 섬유육종 세포주인 WEHI164 세포주와 인체 비소세포 폐암 세포주인 A549 세포주를 배양하여, 먼저 임상에서 흔히 폐암의 항암 화학 요법 치료에 널리 쓰이는 대표적인 topoisomerase II targeted chemotherapeutic drug인 etoposide(VP-16)와 doxorubicin(adriamycin)을 가하였을 때 관찰된 세포 독성을 MTT assay로 측정하고, 각 모세포주(parenta1 cell line)에 TNF-$\alpha$의 유전자를 이입시켜서 형절 변환한 세포주(transformed cell line)에 대하여 각각 동일한 항암제를 가하였을 때 관찰된 세포 독성의 정도를 같은 방법으로 측정하여, 그 결과를 비교 분석하였다. 또한 모세포주에 외부에서 TNF를 가하여 전처치한 후 동일한 항암제를 가하였을 때의 세포독성을 관찰하여 비교 분석하였다. 결과: H2058 세포주에서는 TNF-$\alpha$ 유전자를 이입한 세포주 topoisomerase II targeted drug을 가하였을 때, 항암제 감수성이 모세포주에 같은 항암제를 가하였을 때에 비하여 의미있게 증가함을 관찰할 수 있었으나(p<0.05), WEHI 세포주와 A549 세포주에 있어서는 TNF-$\alpha$ 유전자를 이입한 세포주에서 모세포주에 비하여 항암제 감수성이 증가하지는 않았다. 결론: TNF-$\alpha$ 유전자의 이입이 topoisomerase II targeted chemotherapeutic drug에 대한 항암제 감수성을 증가시키는 효과는 세포주에 따라 다양한 결과를 보이는 것을 알 수 있었으며, 적어도 선택된 특정 종류의 호흡기계 암세포에 있어서는 TNF-$\alpha$ 유전자의 이입으로 항암제 감수성(chemosensitivity)을 증가시킬 수 있을 것으로 사료된다.

• Pediatric Infection and Vaccine
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• 제21권3호
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• pp.225-230
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• 2014

최근 가와사키병에서 tumor necrosis factor-alpha(TNF-alpha) blocker인 infliximab 단일 정주 요법이 불응성 가와사키병 환자들에게 유용한 치료제로 여겨지고 있다. 장기적인 TNF-alpha blocker 사용이 기회감염의 위험을 증가시킬 수 있지만, 가와사키병 환자들에게 infliximab 사용이 심각한 부작용을 초래하지 않으며 안전하게 사용된 증례들이 보고된 바 있다. 불응성 가와사키병을 앓고 있는 5개월 된 영아에서 infliximab (5 mg/kg) 단일 정주 요법을 사용하였고 가와사키 증상이 호전되었으나 infliximab 치료 후 Acinetobacter lwoffii에 의한 패혈증이 발생하였다. 그래서 저자들은 불응성 가와사키병을 앓은 영아에서 infliximab 치료 후 발생한 패혈증의 첫 사례를 보고하며 infliximab 치료 선택에 있어 기회 감염의 위험성에 대해 고려할 것을 당부하는 바이다.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.283-287
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• 2003

While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.

• 동의신경정신과학회지
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• 제10권1호
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• pp.109-119
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• 1999

We investigated whether an aqueous extract of Chong-Myung-Tang inhibits secretion of tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$ from primary cultures of mouse astrocytes. Chong-Myung-Tang dosedependently inhibited the $TNF-{\alpha}$ secretion by astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). Interleukin-1 (IL-1) has been shown to elevate $TNF-{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore investigated whether IL-1 mediated inhibition of $TNF-{\alpha}$ secretion from astrocytes by Chong-Myung-Tang. Treatment of Chong-Myung-Tang to astrocytes stimulated with both LPS and SP decreased IL-1 secretion. Moreover, incubation of astrocytes with IL-1 antibody abolished the synergistic cooperative effect of LPS and SP. These results suggest that Chong-Myung-Tang may inhibits $TNF-{\alpha}$ secretion by inhibiting IL-1 secretion and that Chong-Myung-Tang has a antiinflammatory activity in the central nervous system.

• 대한본초학회지
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• 제34권1호
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• pp.51-57
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• 2019

Objectives : Nypa fruticans Wurmb. (NF) have been used as a traditional medicine to treat inflammatory diseases in East-South Asia. However, it is largely undiscovered whether NF water extract could exhibit anti-inflammatory activities against tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced inflammatory responses on human keratinocytes, HaCaT cells. Therefore, this study was aimed to investigate the anti-inflammatory activity of NF water extract on TNF-${\alpha}$-induced inflammatory responses in HaCaT cells. Methods : To investigate the anti-inflammatory activites of NF water extract in HaCaT cells, the inflammatory model of HaCaT cells was established under a suitable concentration (10 ng/ml) of human TNF-${\alpha}$ (hTNF-${\alpha}$). HaCaT keratinocyte cells were pre-treated with NF water extract for 1 h, and then stimulated with hTNF-${\alpha}$. Then, the cells were harvested to measure the inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$), and pro-inflammatory cytokine including TNF-${\alpha}$ and interleukin (IL)-6. In addition, we examined the inhibitory mechanisms of NF, mitogen activated protein kinases (MAPKs) and inhibitory kappa B alpha ($I{\kappa}-B{\alpha}$) Results : The treatment of NF inhibited the hTNF-${\alpha}$-induced elevation of iNOS, COX-2, and $PGE_2$ in HaCaT cells. In addition, NF treatment inhibited the hTNF-${\alpha}$-induced elevation of TNF-${\alpha}$ and IL-6. Furthermore, NF treatment inhibited the activation of MAPKs but not degradation of $I{\kappa}-B{\alpha}$. Conclusions : Taken together, our result suggest that treatment of NF could inhibit the hTNF-${\alpha}$-induced inflammatory responses via deactivation of MAPKs in HaCaT cells. This study could suggest that NF could be a beneficial agent to prevent skin damage or inflammation.

• 생약학회지
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• 제34권3호통권134호
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• pp.210-217
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• 2003

Korean mistletoe (Viscum album) extract has been found to posses immunostimulatory activity. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to know whether this extract might activate mouse splenic macrophages to produce tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}$) and might play a role in anticancer. To know the effect of M11C on the production of $TNF-{\alpha}$, the splenic macrophages were treated by the M11C, and then collected the supernatant (M11C stimulated splenic macrophage-conditioned media; MSCM). MSCM was analyzed for the $TNF-{\alpha}$ secretion by means of ELISA and immunoblotting, and mRNA expression was analyzed by RT-PCR. The S-180 murine sarcoma model was established to know the effect of M11C on the inhibition of tumor growth. M11C had the effect of $TNF-{\alpha}$ production from splenic macrophages performed by ELISA technique. This ELISA data was reconfirmed by immunoblotting assay. The effects of M11C on the expression of $TNF-{\alpha}$ mRNA from the macrophages was also shown. M11C also had the inhibitory effect of S-180 tumor growth. These data suggest that Korean mistletoe extract M11C may be used for an immunomodulator.

• 대한수의학회지
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• 제57권3호
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• pp.197-200
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• 2017

This study evaluated the effect of a combination of acetaminophen and vitamin C (CAV) on reducing serum cortisol and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) concentrations in piglets vaccinated with foot-and-mouth disease (FMD) vaccine. Piglets were vaccinated with FMD vaccine and treated with CAV at concentrations of 0.0, 0.5, 1.0, and 2.0 kg/ton feed (P-CON, AD-1, AD-2, and AD-3, groups, respectively) for 5 days post-vaccination. Cortisol and $TNF-{\alpha}$ levels at 5 days post-treatment in the AD-1-3 groups were significantly lower than that in the P-CON group (p < 0.05). There were no significant differences between AD-2 and AD-3 groups and non-vaccinated, non-CAV-treated piglets.

• Journal of Evidence-Based Herbal Medicine
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• 제1권1호
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• pp.7-11
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• 2008

The purpose of this study was to investigate the anti-inflammatory effects of extract from Hwang lyun tang (HLT) on the THP-1 cell and HMC-1 cell. To evaluate of anti-inflammatory of HLT, we examined cytokines production in lipopolysacchride (LPS)-induced THP-1 cell and A23187, PMA-induced HMC-1 cell. Extract of HLT inhibit LPS-induced interleukin (IL)-8 production in human monocyte THP-1 cells. Extract of HLT inhibit A23187, PMA-induced IL-8, tumor necrosis factor-$\alpha$ (INF-$\alpha$) production in HMC-1 cells. HLT down-regulated LPS-induced IL-8 production and A23187, PMA-induced IL-8, TNF-$\alpha$ production, which may be provide a clinical basis for anti-inflammatory properities of HLT.

• Journal of Evidence-Based Herbal Medicine
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• 제1권1호
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• pp.1-5
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• 2008

Objectives : The purpose of this study was to investigate the anti-inflammatory effects of extract from Jak-Yak Tang (JYT) on the THP-1 cell and HMC-1 cell. Method : To evaluate of anti-inflammatory of JYT, we examined cytokines production in lipopolysacchride (LPS)-induced THP-1 cell and A23187, PMA-induced HMC-1 cell. Result : Extract of JYT inhibit LPS-induced interleukin (IL)-8 production in human monocyte THP-1 cells. Extract of JYT inhibit A23187, PMA-induced IL-8, tumor necrosis factor-$\alpha$ (INF-$\alpha$) production in HMC-1 cells. Conclusion : NT down-regulated LPS-induced IL-8 production and A23187, PMA-induced IL-8, TNF-$\alpha$ production, which may be provide a clinical basis for anti-inflammatory properities of JYT.

• Clinical and Experimental Pediatrics
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• 제57권10호
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• pp.440-444
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• 2014

Purpose: Febrile seizures are induced by fever and are the most common type of seizures in children. Although numerous studies have been performed on febrile seizures, their pathophysiology remains unclear. Recent studies have shown that cytokines may play a role in the pathogenesis of febrile seizures. The present study was conducted to identify potential links between serum interleukin-1beta (IL-$1{\beta}$), tumor necrosis factor-alpha (TNF-${\alpha}$), and febrile seizures. Methods: Ninety-two patients with simple or complex febrile seizures (46 patients per seizure type), and 46 controls with comparable age, sex, and severity of temperature were enrolled. Results: The median concentrations of serum IL-$1{\beta}$ in the simple, complex febrile seizure, and control groups were 0.05, 0.1, and 0.67 pg/mL, respectively (P=0.001). Moreover, the median concentrations of TNF-${\alpha}$ in the simple, complex febrile seizure, and control groups were 2.5, 1, and 61.5 pg/mL, respectively (P=0.001). Furthermore, there were significant differences between the case groups in serum IL-$1{\beta}$ and TNF-${\alpha}$ levels (P<0.05). Conclusion: Unlike previous studies, our study does not support the hypothesis that increased IL-$1{\beta}$ and TNF-${\alpha}$ production is involved in the pathogenesis of febrile seizures.