• 제목/요약/키워드: tumor necrosis factor $(TNF)-{\alpha}$

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Streptozotocin으로 당뇨가 유도된 C57BL/6 생쥐 지방조직에서의 염증성 사이토카인 유전자의 이상발현 (Altered Gene Expression of Inflammatory Cytokines in Adipose Tissue of Streptozotocin-induced Diabetic C57BL/6 Mice)

  • 이용호;김종봉
    • 생명과학회지
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    • 제23권6호
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    • pp.825-831
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    • 2013
  • 본 연구를 통하여 streptozotocin 주사에 의한 당뇨 유발이 일반식이와 고지방식이로 키운 C57BL/6 수컷생쥐의 지방조직에서의 염증성 사이토카인 유전자 발현에 미치는 영향을 조사하였다. 네 그룹의 당뇨생쥐(일반식이 또는 고지방식이로 키운 16주령 또는 26주령 생쥐)와 네 그룹의 비당뇨 대조군을 포함한 모두 73마리의 생쥐가 이 실험에 사용되었다. Real-time PCR을 이용하여 지방조직에서의 tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)와 monocyte chemoattractant protein-1 (MCP-1)의 유전자 발현량을 측정한 결과, TNF-${\alpha}$ mRNA는 당뇨 유발에 의해 증가하는 양상을 보였다. 특히, 16주령의 일반식이 생쥐의 경우 비당뇨 대조군에 비해 당뇨가 유발된 실험군에서 유의한 증가가 관찰되었다. MCP-1 mRNA 발현은 STZ처리에 따른 당뇨유발에 의해 감소하는 경향을 나타내었다. 특히, 16주령 고지방식이의 당뇨 실험군에서의 발현이 비당뇨 대조군에서의 발현량의 26%에 해당할 정도로 큰 감소를 나타내었다. 또한, MCP-1의 발현은 인슐린 농도와 유의한 상관관계가 있음이 확인되었다. 이들 실험결과는 당뇨 모델 생쥐에서 지방조직의 염증성 사이토카인이 이상발현되고 있음을 나타내며, 비만, 인슐린저항성, 및 당뇨에서의 저준위 염증상태와 지방조직에서의 염증성 사이토카인 발현 조절의 기작을 밝히는데 유용한 정보를 제공할 것으로 기대된다.

Tumor Necrosis Factor-alpha and Apoptosis Following Spinal Nerve Ligation Injury in Rats

  • Kim, Sung-Hoon;Nam, Jae-Sik;Choi, Dae-Kee;Koh, Won-Wook;Suh, Jeong-Hun;Song, Jun-Gol;Shin, Jin-Woo;Leem, Jeong-Gil
    • The Korean Journal of Pain
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    • 제24권4호
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    • pp.185-190
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    • 2011
  • Background: Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-${\alpha}$ and the extent of apoptosis in the dorsal root ganglion after SNL in rats. Methods: Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-${\alpha}$ protein levels in the L5.6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3. Results: SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-${\alpha}$ protein levels were increased in the DRG in rats that had undergone SNL ($12.7{\pm}3.2$ pg/100 ${\mu}g$, P < 0.001) when compared with naive rats ($4.1{\pm}1.4$ pg/100 ${\mu}g$). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naive rats (P < 0.001, P < 0.05, respectively). Conclusions: SNL injury produces mechanical and cold allodynia, as well as TNF-${\alpha}$ elevation and apoptosis in the DRG.

Diagnosis and Treatment of Latent Tuberculosis Infection due to Initiation of Anti-TNF Therapy

  • Shim, Tae Sun
    • Tuberculosis and Respiratory Diseases
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    • 제76권6호
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    • pp.261-268
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    • 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.

Fucoidan에 의한 개 말초혈액 단핵구세포에서 생산된 TNF-${\alpha}$의 다형핵백혈구에 대한 탐식능과 순간산소과소비력의 증가효과 (Fucoidan Increases Phagocytic Capacity and Oxidative Burst Activity of Canine Peripheral Blood Polymorphonuclear Cells Through TNF-${\alpha}$ from Peripheral Blood Mononulear Cells)

  • 김수현;강지훈;양만표
    • 한국임상수의학회지
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    • 제28권2호
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    • pp.183-189
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    • 2011
  • 개 말초혈액 다형핵 백혈구(PMNs)의 탐식능력과 순간산소과소비력 (OBA) 에 대한 fucoidan의 효과를 검토하였다. Fucoidan 그 자체는 PMNs의 탐식능력과 OBA에 직접적인 효과를 보이지 않았다. 그러나 fucoidan으로 배양한 PBMCs의 배양상층액은 PMNs의 탐식능력과 OBA를 농도의존적으로 증가시켰다. 또한, TNF-${\alpha}$에 의한 PMNs의 탐식능력과 OBA의 측정 결과도 fucoidan으로 배양한 PBMCs 배양상층액의 그것과 유사하였다. 이러한 탐식능력과 OBA의 활성은 anti-TNF-${\alpha}$ pAb를 처리했을 때 억제되었다. PBMCs 배양 상층액 속의 TNF-${\alpha}$의 양을 정량한 결과 대조군에 비해 증가되었으며, PBMCs의 TNF-${\alpha}$ mRNA 발현 정도도 fucoidan을 첨가한 경우 증가되었다. 이상의 결과로부터, fucoidan은 개 말초혈액 PMNs의 탐식능력과 OBA에 대하여 면역자극 작용을 가지고 있으며, 이것은 fucoidan의 자극에 의해 PBMCs에서 생산되어 분비되는 가용성 물질인 TNF-${\alpha}$에 의해 나타나는 것으로 사료되었다.

오미소독음(五味消毒飮)의 항염효과(抗炎效果) 및 기전(機轉)에 관(關)한 실험적연구(實驗的硏究) (Anti-inflammatory Effects of Omisodokeum)

  • 서윤정;김송백;조한백;최창민;이순이
    • 대한한방부인과학회지
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    • 제21권1호
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    • pp.39-54
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    • 2008
  • Purpose: The purpose of this study was to investigate the anti-inflammatory effects of the water extract of Omisodokeum (OMSDE) on peritoneal macrophages, Methods: To verify the anti-inflammatory mechanism of OMSDE, the activation of nuclear $factor-{\kappa}B$ $(NF-{\kappa}B)$ and the phosphorylation of MAPK were examined. Results: The extract of OMSDE suppressed the production of LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6 and IL-12 in the macrophages. OMSDE inhibited the degradation of inhibitory ${\kappa}B-{\alpha}$ $(I{\kappa}B-{\alpha})$ and it suppressed the activation of extracellular signal-regulated kinase (ERK 1/2) but didn't inhibit c-Jun N-terminal kinase (JNK) and p38, indicating that OMSDE may inhibit the pro-inflammatory cytokine production process by inhibiting the activation of $NF-{\kappa}B$ and ERK 1/2. Furthermore, OMSDE inhibited the production of interferon $(IFN)-{\beta}$ but didn't inhibit of $IFN-{\alpha}$ in the LPS-stimulated macrophages through the down-regulation of interferon regulatory factor (IRF)-1 and IRF-7. The Oral administration of OMSDE inhibited LPS-induced endotoxin shock and the production of $TNF-{\alpha}$ in serum but didn't inhibit of $IL-1{\beta}$ and IL-6. Conclusion: These results suggest that OMSDE may be effective in the prevention and treatment of inflammatory diseases.

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Effects of Omega-3-Rich Harp Seal Oil on the Production of Pro-Inflammatory Cytokines in Mouse Peritoneal Macrophages

  • Choi, Myungwon;Ju, Jaehyun;Suh, Jae Soo;Park, Kun-Young;Kim, Kwang Hyuk
    • Preventive Nutrition and Food Science
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    • 제20권2호
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    • pp.83-87
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    • 2015
  • Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-${\alpha}$, interleukin-(IL)-$1{\beta}$, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-$1{\beta}$, TNF-${\alpha}$, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-${\alpha}$, IL-$1{\beta}$, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-$1{\beta}$, TNF-${\alpha}$, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.

강활에서 종양괴사인자 생성을 억제하는 활성성분의 분리 (Isolation of Inhibitory Components on Tumor Necrosis Factor-${\alpha}$ Production from Angelica koreana)

  • 조재열;이종수;박지수;박명환
    • 약학회지
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    • 제42권2호
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    • pp.125-131
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    • 1998
  • The total ethanol extract of Angelica koreana radix (UmbeUiferae) showed potent inhibitory effect on tumor necrosis factors (TNF-${\alpha}$) production from LPS-stimulated RAW 264.7 cells in screening studies on 118 Korean medicinal plants. The activity-guided fractionation of the total ethanol extract resulted in the isolation of 4 compounds, including active substances. The chemical structures of the compounds isolated were established by chemical and spectrometric analyses as imperatorin, isoimperatorin, osthol and oxypeucedanin. Among them, osthol, oxypeucedariin and isoimperatorin showed significant inhibitory activities on TNF-${\alpha}$ production as 54.3${\pm}$2.1%, 33.6${\pm}$1.0% and 17.7${\pm}$3.0%, respectively, at 12.5${\mu}$g/ml.

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Production of superoxide anion, nitric oxide and tumor necrosis factor-$\alpha$ by cultured murine peritoneal leukocytes is inhibited by taurine chloramine

  • Kim, Chaekyun;Park, Eunkyue;Michael R. Quinn
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.177-177
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    • 1996
  • Taurine Chloramine (Tau-Cl) inhibits production of nitric oxide(NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) in activated peritoneal macrophages, similar In that previously reported for activated RAW 264.7 cells. In addition, the effect of Tau-Cl and taurine on superoxide anion (O$\_$2/$\^$-/) Production in murine peritoneal exudate polymorphonuclear leukocytes (PMN) was examined. Tau-Cl inhibited O$\_$2/$\^$-/ production in a manner that was dose-dependent and reversible, Taurine also inhibited O$\_$2/$\^$-/ production by stimulated PMN, but at higher concentrations and to a lesser extent than Tau-Cl. The effects of taurine on O$\_$2/$\^$-/ production was attributed to the in vitro formation of Tau-Cl catalyzed by PMN associated halide-dependent myeloperoxidase. In contrast, production of NO and TNF-${\alpha}$ by activated peritoneal exudate macrophages was inhibited by Tau-Cl while taurine was without effect. These data lend support to the notion that Tau-Cl may participate ill the inflammatory responses by modulating production of inflammatory mediators.

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Identification of tumor necrosis factor-${\alpha}$ levels around miniscrews during canine distalization

  • Kaya, Filiz Acun;Hamamcl, Nihal;Uysal, Ersin;Yokus, Beran
    • 대한치과교정학회지
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    • 제41권1호
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    • pp.36-41
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    • 2011
  • Objective: The aim of this study was to measure tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) levels around miniscrews used for anchorage during a 3-month period of canine distalization. Methods: Sixteen patients (8 boys, 8 girls; mean age, $16.6{\pm}2.4$ years) whose upper first premolars were extracted for orthodontic treatment were included in this study. Miniscrews were used as an anchorage unit in canine distalization. Thirty-two (32) miniscrew implants were placed bilaterally in the alveolar bone between the maxillary second premolars and first molars. The treatment, miniscrew, and control groups comprised upper canines, miniscrew implants, and upper first premolars, respectively. Peri-miniscrew implant crevicular fluid and gingival crevicular fluid were obtained before applying force and at 1, 24, and 48 hours, and at 7 and 21 days, and 3 months after applying force. Results: During the 3-month period, the (TNF-${\alpha}$) levels increased significantly at 24 hours only in the treatment group (p < 0.01). In the miniscrew and control groups, there were no statistically Significant changes. No significant differences were observed between groups. Conclusions: Miniscrews can be conveniently used for anchorage in orthodontics.

Matrix Metalloproteinase Inhibitors Attenuate Neuroinflammation Following Focal Cerebral Ischemia in Mice

  • Park, Cheol-Hong;Shin, Tae-Kyeong;Lee, Ho-Youn;Kim, So-Jung;Lee, Won-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • 제15권2호
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    • pp.115-122
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    • 2011
  • The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-${\alpha}$, and IDO, thereby providing a therapeutic benefit against cerebral ischemia.