• Tuberculosis and Respiratory Diseases
• /
• 제76권6호
• /
• pp.261-268
• /
• 2014

Patients with immune-mediated inflammatory diseases (IMIDs) are increasingly being treated with anti-tumor necrosis factor (TNF) agents and are at increased risk of developing tuberculosis (TB). Therefore, diagnosis and treatment of latent TB infection (LTBI) is recommended in these patients due to the initiation of anti-TNF therapy. Traditionally, LTBI has been diagnosed on the basis of clinical factors and a tuberculin skin test. Recently, interferon-gamma releasing assays (IGRAs) that can detect TB infection have become available. Considering the high-risk of developing TB in patients on anti-TNF therapy, the use of both a tuberculin skin test and an IGRA should be considered to detect and treat LTBI in patients with IMIDs. The traditional LTBI treatment regimen consisted of isoniazid monotherapy for 9 months. However, shorter regimens such as 4 months of rifampicin or 3 months of isoniazid/rifampicin are increasingly being used to improve treatment completion rates. In this review, the screening methods for diagnosing latent and active TB before anti-TNF therapy in patients with IMIDs will be briefly described, as well as the current LTBI treatment regimens, the recommendations for managing TB that develops during anti-TNF therapy, the necessity of regular monitoring to detect new TB infection, and the re-initiation of anti-TNF therapy in patients who develop TB.

• Journal of Ginseng Research
• /
• 제33권1호
• /
• pp.1-7
• /
• 2009

우리 몸의 많은 기관을 비롯하여 장기들은 반복적이거나 혹은 급성 스트레스를 이겨내지 못하고 만성 스트레스로 이어질 경우 질병이 생기게 된다. 특히 강하고 지속적인 스트레스에 노출되면 뇌의 해마 수지상 세포(hippocampal dendrites)가 위축되거나 크기가 작아진다. 이렇게 스트레스로 인하여 증가된 글루코 코티코이드 호르몬은 뉴런 흥분제인 glutamate를 유도하거나 에너지 대사를 변형시켜 신경 독작용을 일으킨다. 이러한 연속적인 반응은 TNF-$\alpha$ convertase(TACE)를 활성화시켜 TNF-$\alpha$가 분비되도록 하여 전사 조절자인 NF-${\kappa}B$가 핵내로 전이되고 신경 손상을 일으키는 iNOS와 COX-2와 같은 효소를 유도한다. 이런 산화적 스트레스의 상위조절인자 TACE는 스트레스에 의한 여러 가지 염증성 질환 및 숙주방어에서 가장 중요한 조절자인 TNF-alpha를 수용체로부터 "유리(shedding)" 시키는 역할을 한다. 따라서 이런 신호 전달계를 자극하는 TACE의 발현 양과 이로 인한 지속적인 처리과정이 중요한 문제로 대두되고 있다. 특히 여러 스트레스 중에서 고정화 스트레스 및 신체적 구속 스트레스에 대한 연구는 뇌에서 산화물 생성을 증가시키지만 인삼이 뇌의 산화물질 생성에 어떤 영향을 미치는지 체계적인 연구가 진행된 바 없다. 따라서 염증을 매개하는 TNF-alpha의 생산에 중요한 역할을 하는 TACE의 발현 조절 및 TNF-alpha 신호전달을 연구함으로써 인삼의 항산화 기전을 분자 수준에서 규명할 수 있게 될 것으로 기대된다.

• BMB Reports
• /
• 제35권3호
• /
• pp.267-272
• /
• 2002

TNF-$\alpha$ elicits various responses including apoptosis, proliferation, and differentiation according to cell type. In neuronal PC12 cells, TNF-$\alpha$ induces moderate apoptosis while lipopolysarccaharide or trophic factor deprivation can potentiate apoptosis that is induced by TNF-$\alpha$. TNF-$\alpha$ initiates various signal transduction pathways leading to the activation of the caspase family, NF-${\kappa}B$, Jun N-terminal kinase, and p38 MAPK via the death domain that contains the TNF-$\alpha$ receptor. Inhibition of translation using cycloheximide greatly enhanced the apoptotic effect of TNF-$\alpha$. This implies that the induction of anti-apoptotic genes for survival by TNF-$\alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic genes for survival by TNF-$\alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic Bcl-2 family member, was highly expressed in response to TNF-$\alpha$. In this study, we examined the anti-apoptotic role of p38 MAPK that is activated by TNF-$\alpha$ in neuronal PC12 cells. The phosphorylation of p38 MAPK in response to TNF-$\alpha$ slowly increased and lasted several hours in the PC12 cell and DRG neuron. This specific inhibitor of p38 MAPK, SB202190, significantly enhanced the apoptosis that was induced by TNF-$\alpha$ in PC12 cells. This indicates that the activation of p38 MAPK could protect PC12 cells from apoptosis since there is no known role of p38 MAPK in resoonse to TNF-$\alpha$ in neuron. This discovery could be evidence for the neuroprotective role of the p38 MAPK.

• Journal of Dairy Science and Biotechnology
• /
• 제25권2호
• /
• pp.1-4
• /
• 2007

본 연구는 양(羊)의 초유(初乳)에 발현시킨 $TNF-{\alpha}$ 항체를 이용하여 염증반응에서 생성된 $TNF-{\alpha}$의 활성억제를 통한 염증반응 완화능을 세포단계의 생물검정과 장 염증이 유도된 동물모델을 통해 검증하였다. 실험 결과, 면역반응을 통해 생성된 양(羊)의 초유(初乳)에 함유된 $TNF-{\alpha}$ 항체는 WEHI-13 VAR 세포의 $TNF-{\alpha}$ 활성을 유의적으로 억제함을 확인할 수 있었다. 동물실험 1의 경우, 예상되는 $TNF-{\alpha}$ 항체의 염증반응 억제 효과보다 유도된 염증반응의 정도가 강하였고, 동물실험 2의 경우 대장염 유도에 대해 실험동물간의 민감성 차이를 나타내었다.

• 한방재활의학과학회지
• /
• 제24권3호
• /
• pp.99-110
• /
• 2014

Objectives The purpose of this study was to investigate the Anti-oxidation and anti-inflammatory effects of ethanol extract from asiasari radix (AR) on lipopolysaccharide (LPS)-induced in RAW 264.7 Cells Methods Anti-oxidative effects of AR were measured by scavenging activities of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and production of reactive oxygen species (ROS) in RAW 264.7 cells. Anti-inflammatory effects of AR were measured by mediators including nitric oxide(NO), interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necosis factors-${\alpha}$ (TNF-${\alpha}$) and iNOS, IL-$1{\beta}$, IL-6, TNF-${\alpha}$ mRNA expression in RAW 264.7 cells. Results Total phenolic content was expressed $28.77{\pm}1.67$. DPPH radical Scavenging was increased depend on AR ethanol extract. ABAT radical Scavenging was increased depend on AR ethanol extract. Production of ROS was significantly decreased by AR ethanol extract on concentration of 100 (${\mu}g/ml$). Production of NO was significantly decreased by AR ethanol extract on concentration of $100({\mu}g/ml)$. Production of IL-$1{\beta}$, interleukin-6 and TNF-${\alpha}$ were increased depend on AR ethanol extract. And Production of interleukin-6, TNF-${\alpha}$ were significantly decreased AR ethanol extract. iNOS, IL-$1{\beta}$, IL-6, TNF-${\alpha}$ mRNA expression of RAW 264.7 cells was increased depend on AR ethanol extract. Conclusions According to this study, AR ethanol extract has anti-oxidative and anti-inflammatoy effects.

• 한국약용작물학회지
• /
• 제18권2호
• /
• pp.105-112
• /
• 2010

Korean Sophora japonica has been found to posses an anti-inflammatory activity. In this study, Korean Sophora japonica extract, rutin, was used to know whether rutin inhibits to produce inflammatory mediators NO and TNF-$\alpha$ from the mouse peritoneal macrophages that were treated an inflammatory agent LPS. The rutin-1 hr pretreated macrophages were incubated with LPS for 0.5~5 hrs, and then collected the supernatant and the cell lysate for measurements of the level of iNOS, NO, TNF-$\alpha$ mRNA, TNF-$\alpha$, and p-NF-${\kappa}B$. Minimal and maximal effective doses of the rutin on them were 1 and $100{\mu}g/ml$, respectively. The maximal effective dose of rutin certainly inhibted the productions of iNOS, NO, TNF-$\alpha$ mRNA, TNF-$\alpha$and p-NF-${\kappa}B$ from the LPS-treated macrophages (p<0.0001). Its $ED_{50}$ for inhibition of TNF-$\alpha$ mRNA and p-NF-${\kappa}B$ was $5{\mu}g/m{\ell}$, and for iNOS, NO, and TNF-$\alpha$ was $10{\mu}g/m{\ell}$. The rutin did not have any cytotoxic effect. As the results, the Sophora japonica rutin could be a good candidate for an anti-inflammatory action.

• Journal of Rheumatic Diseases
• /
• 제24권4호
• /
• pp.227-235
• /
• 2017

Objective. Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. Methods. Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. Results. Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34, $-1.63{\pm}0.30$ vs. n=31, $-2.05{\pm}0.34$) and standard population set analysis (n=31, $-1.51{\pm}0.29$ vs. n=24, $-2.21{\pm}0.34$). Similarly, the change in DAS28 at 12 months did not reach statistical significance ($-1.82{\pm}0.35$ in the rituximab vs. $-2.34{\pm}0.44$ in the alternative anti-TNF agents, p=0.2390). Furthermore, the incidences of adverse events were similar between two groups (23.5% for rituximab group vs. 25.8% for alternative anti-TNF agents group, p=0.7851). Conclusion. Despite the limitations of our study, switching to rituximab or alternative anti-TNF agents after failure of the initial TNF antagonist showed no significant therapeutic difference in DAS28 reduction.

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

• 생약학회지
• /
• 제42권3호
• /
• pp.253-259
• /
• 2011

Macrophages play a vital role in the innate immune system involving defensive cytokines such as TNF (tumor necrosis factor)-${\alpha}$ and nitric oxide (NO). Therefore, we try to elucidate the anti-inflammatory activity of Chaga mushroom (Inonotus Obliquus, IO) in murine macrophages. Raw 264.7 cells and peritoneal macrophages of mice were cultured with or without LPS/LPS + IFN-${\gamma}$ in the presence of IO aqueous extracts (IOE 0.2, 2, 20, 100 ${\mu}g$/mL) for 24 hr and 48 hr, respectively. Exposure of IOE caused the decrease of NO production and increase of TNF-${\alpha}$ production in dose-dependent manner in activated peritoneal macrophage in vitro. To further investigate anti-inflammatory effects of IO ex vivo, we orally administrated capsaicin (PC, 3 mg/kg/day) and IOE (100, 200, 400 mg/kg/day) for 4 consecutive days to C57BL/6 mice (7~9 weeks old, female), then observed the NO secretion and cytokine (TNF-${\alpha}$) production of LPS/LPS + INF-${\gamma}$-stimulated peritoneal macrophages. IOE inhibits NO secretion in dose-dependent manner both ex vivo and in vitro and increases the production of TNF-${\alpha}$ in vitro. In addition, we found that IOE possessed suppressive effects of LPS-stimulated TNF-${\alpha}$, IL-$1{\beta}$, COX-2, as well as iNOS expressions in Raw 264.7 cells. These findings indicate that IOE suppress not only the LPS-induced NO overproduction of murine peritoneal macrophages, but also iNOS, COX-2, TNF-${\alpha}$, and IL-$1{\beta}$ overexpression of LPS-induced Raw 264.7 cells. Consequently, our results suggest that IO may have the anti-inflammatory effects via suppression of the inflammatory cytokines and mediators, and be useful for the treatment of inflammatory diseases.

• IMMUNE NETWORK
• /
• 제11권1호
• /
• pp.42-49
• /
• 2011

Background: In this study, we have investigated the effect of Korean red ginseng (KRG) extracts on the production of TNF-${\alpha}$ and IL-8 in human keratinocytes. Also, to examine the antioxidative effect of red ginseng extracts, free radical scavenging activity and superoxide dismutase (SOD) activity in human dermal fibroblasts was measured. Methods: To investigate the effect of KRG in atopic dermatitis, we measured the level of TNF-${\alpha}$ and IL-8 secretion in LPS-stimulated human keratinocytes after the treatment of KRG extracts using enzyme-linked immunosorbent assay. Anti-oxidative activity was investigated by measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and SOD activity. Results: The stimulation of human keratinocytes with KRG extracts shifted the LPS-induced cytokine secretion toward a more immunosuppressive response. KRG dose-dependently decreased TNF-${\alpha}$ and IL-8 production in HaCaT cells and a significant inhibition of TNF-${\alpha}$ was shown when cells were treated with 500 and $1,000{\mu}g/ml$ of KRG extracts. Additionally, KRG extracts showed DPPH radical scavenging and SOD activity in a dose-dependent manner. Particularly, SOD activities of concentrations higher than $60{\mu}g/ml$ of KRG extracts were significantly different in human dermal fibroblast cells. Conclusion: Based on this study, KRG extracts may be a useful immunosuppressive agent in the treatment of atopic dermatitis.