• 생명과학회지
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• 제16권7호
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• pp.1207-1213
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• 2006

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$는 염증성 골질환에서의 골조직의 손실과 밀접한 관련이 있다. 본 연구에서는 인체 골수 유래 중간엽 줄기세포의 골세포로의 분화과정에 대한 $TNF-{\alpha}$의 영향을 조사하였다. $TNF-{\alpha}$는 골수 유래 중간엽 줄기세포의 골세포로의 분화를 나타내는 표시인 세포외 무기질 축적과 alkaline phosphatase의 발현의 증가를 일으켰으며 2ng/ml의 농도에서 최대의 증가를 나타내었다. $TNF-{\alpha}$에 의한 골세포로의 분화는 $NF_kB$의 저해제에 의해서는 영향받지 않았으나 JNK 특이 저해제인 SP600125에 의해 완벽하게 억제되었다. 이는 $TNF-{\alpha}$에 의한 골수 유래 중간엽 줄기세포의 골세포로의 분화과정에 JNK가 중요한 역할을 한다는 것을 제시한다.

• BMB Reports
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• 제42권5호
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• pp.260-264
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• 2009

Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) exhibits cytotoxicity towards various tumor cells in vitro and induces apoptotic necrosis in transplanted tumors in vivo. It also shows severe toxicity when used systemically for the treatment of cancer patients, hampering the development of TNF-$\alpha$ as a potential anticancer drug. In order to understand the structure-function relation of TNF-$\alpha$ with respect to receptor binding, we selected four regions on the bottom of the TNF-$\alpha$ trimer that are in close contact with the receptor and carried out mutagenesis studies and computational modeling. From the study, various TNF-$\alpha$ muteins with a high therapeutic index were identified. These results will provide a structural basis for the design of highly potent TNF-$\alpha$ for therapeutic purposes. By conjugating TNF-$\alpha$ muteins with a high therapeutic index to a fusion partner, which targets a marker of angiogenesis, it could be possible to develop TNF-$\alpha$ based anticancer drugs.

• 생명과학회지
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• 제17권1호
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• pp.45-50
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• 2007

세포 배양액에 tetracycline이 없는 경우 FADD를 발현하면서 사멸하는 평활근세포 (FADD-SMC)에서 분비하는 $TNF-\alpha$의 활성을 조사하였다. 배양액에 tetracycline이 없는 경우 FADD-SMC는 약 1000 pg/ml의 $TNF-\alpha$를 분비하였다. $TNF-\alpha$를 포함하는 배양액을 분리하고, 이 배양액을 정상세포에 처리한 결과 인산화한 p38 MAPK와 nuclear, factor, kappa B (NF-kB)의 활성이 증가하였다. 또한 이 배양액을 L929 세포에 처리하는 경우 세포독성이 발생하였다. NF-kB, p38 MAPK 그리고 L929 세포에 대찬 효과는 배양액에서 suluble TNF receptor를 이용하여 $TNF-\alpha$를 제거하는 경우 감소하였다.

• 한국임상수의학회지
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• 제37권5호
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• pp.249-254
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• 2020

Neutrophil extracellular trap (NET) formation is an immune response for the invasion of microbes. The purpose of this study is to examine the effect of zinc on NET formation of porcine peripheral blood polymorphonuclear cells (PMNs). The NET formation of PMNs was measured by fluorescence microplate reader. The production of tumor necrosis factor (TNF)-α in the culture supernatants from zinc-treated peripheral blood mononuclear cells (PBMCs) was measured by enzyme-linked immunosorbent assay (ELISA). Zinc itself did not have no effect on NET formation. However, the NET formation of PMNs was increased by culture supernatants from PBMCs treated with zinc. Also, the NET formation of PMNs was increased by recombinant porcine (rp) TNF-α. The production of TNF-α in PBMCs culture supernatants was shown to increase upon zinc treatments. These NET formations of PMNs increased by either culture supernatant from PBMCs treated with zinc or rpTNF-α were inhibited by treatment of anti-rpTNF-α polyclonal antibody (pAb). These results suggested that zinc has an immunostimulating effect on the NET formation of PMNs, which is mediated by TNF-α released from zinc-treated PBMCs. Therefore, zinc may play an important role for NET formation in the defense of porcine inflammatory diseases.

• 생명과학회지
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• 제29권11호
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• pp.1251-1257
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• 2019

본 연구에서는 펩티도글리칸이 단핵세포의 $TNF-{\alpha}$ 발현에 미치는 영향을 조사하였고, 또한 펩티도글리칸에 의한 $TNF-{\alpha}$ 발현에 관련된 세포의 요소들을 연구하였다. 사람의 단핵세포주인 THP-1 세포를 펩티도글리칸에 노출시키는 경우 $TNF-{\alpha}$ 분비 증가뿐만 아니라 $TNF-{\alpha}$ 유전자 전사를 유도하는 결과를 가져왔다. TLR-2/4의 억제제인 OxPAPC은 펩티도글리칸에 의한 $TNF-{\alpha}$의 발현을 저해하였다. 그리고 U0126, SB202190, SP6001250, LY294002, Akti IV, rapamycin, NAC, DPI 같은 약리학적 저해제 또한 $TNF-{\alpha}$ 발현을 유전자/단백질 수준에서 상당히 약화시켰다. 그러나 polymyxin B는 $TNF-{\alpha}$ 발현에 영향을 주지않았다. 따라서 펩티도글리칸이 TLR-2, PI3K, Akt, mTOR, MAPKs, ROS 등을 통하여 단핵세포의 $TNF-{\alpha}$ 발현을 증가시킴을 확인하였다.

• 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.

• BMB Reports
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• 제48권10호
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• pp.559-564
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• 2015

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-$\alpha$-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-$\alpha$-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-$\alpha$ significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-$\alpha$-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-$\alpha$-induced invasion of LNCaP cells. Compared to untreated controls, TNF-$\alpha$-stimulated LNCaP cells showed a significant increase in nuclear factor-${\kappa}B$ (NF-${\kappa}B$) luciferase activity. However, mangiferin treatment markedly decreased TNF-$\alpha$-induced NF-${\kappa}B$ luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-${\kappa}B$ subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-${\kappa}B$-mediated MMP-9 expression.

• BMB Reports
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• 제39권1호
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• pp.1-8
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• 2006

Helicobacter pylori is the definitive carcinogen for stomach cancer and is known to induce proinflammatory cytokines, such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1(IL-1) in the stomach. Based on our findings that TNF-$\alpha$ is an endogenous tumor promoter, we identified the TNF-$\alpha$ inducing protein (Tip$\alpha$) gene family, and confirmed Tip$\alpha$ and HP-MP1 as new carcinogenic proteins of H. pylori. Tip$\alpha$ protein is unique to H. pylori, and this paper shows the strong tumor promoting activity of Tip$\alpha$ gene family, in cooperation with Ras protein and its mechanisms of action in relation to NF-${\kappa}B$ activation, and discusses the carcinogenic role of Tip$\alpha$ in stomach cancer. Our recent finding showing that penicillin-binding proteins of other bacteria are weak homologues of Tip$\alpha$ is also discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7831-7834
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• 2014

Objective: To explore the influence of different ways of blood transfusion on the expression levels of interleukins (IL) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) inperi-operative patients with esophageal cancer. Materials and Methods: A total of 80 patients with esophageal cancer who underwent radical operations were selected as study patients and randomly divided into an observation group (treated with autologous blood transfusion) and control group (with homologous blood transfusion). Changes of intra-operative indexes and peri-operative blood indexes, from hemoglobin (Hb) and hematocrit value (Hct), to levels of inflammatory factors like interleukins-6 (IL-6), IL-8, IL-10 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were compared. Results: Operations for patients in both groups were successfully conducted, and no significant differences in mean surgical duration and intra-operative hemorrhage volume, fluid infusion volume and blood transfusion volume were detected (p>0.05). Compared with values before surgery, Hb and Hct levels decreased significantly while white blood cell count (WBC) increased 1, 5 and 7 d after operation (p<0.05, p<0.01). In addition, WBC was apparently higher in observation group than in control group 5 and 7 d after operation (p<0.01). Compared with before surgery, in the observation group, levels of IL-6, IL-8 and IL-10 had no significant differences after operation (P>0.05), but TNF-${\alpha}$ level increased y (p<0.01), whereas in control group, IL-6 level had no significant difference (p>0.05), IL-8 level decreased obviously (p<0.05), IL-10 level increased markedly first and then decreased gradually as time passed but its level remained elevated (p<0.01), and TNF-${\alpha}$ level increased first and then decreased, and there was no significant difference 7 d after operation (p>0.05). Conclusions: Decreased IL-8 and increased IL-10 levels are two important reasons for immunosuppression after homologous blood transfusion, whereas autologous blood transfusion can alleviate this while increasing the TNF-${\alpha}$ level, which also has potential to improve anti-tumor immunity in the human body.

• Molecules and Cells
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• 제45권4호
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• pp.193-201
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• 2022

Excessive production of reactive oxygen species (ROS) is a key phenomenon in tumor necrosis factor (TNF)-α-induced cell death. However, the role of ROS in necroptosis remains mostly elusive. In this study, we show that TNF-α induces the mitochondrial accumulation of superoxide anions, not H₂O₂, in cancer cells undergoing necroptosis. TNF-α-induced mitochondrial superoxide anions production is strictly RIP3 expression-dependent. Unexpectedly, TNF-α stimulates NADPH oxidase (NOX), not mitochondrial energy metabolism, to activate superoxide production in the RIP3-positive cancer cells. In parallel, mitochondrial superoxide-metabolizing enzymes, such as manganese-superoxide dismutase (SOD2) and peroxiredoxin III, are not involved in the superoxide accumulation. Mitochondrial-targeted superoxide scavengers and a NOX inhibitor eliminate the accumulated superoxide without affecting TNF-α-induced necroptosis. Therefore, our study provides the first evidence that mitochondrial superoxide accumulation is a consequence of necroptosis.