• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.332-342
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• 2000

Background : The importance of pro-inflammatory cytokines, especially tumor necrosis factor $\alpha$ (INF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the activation of NF-${\kappa}B$. However, the relationship between pro-inflammatory cytokine expression and NF-${\kappa}B/I{\kappa}B$ pathway in lung epithelial cells is not clear. Methods : BEAS-2B, A549, Na-H157, NCI-H719 cells were stimulated with IL-$1{\beta}$ or TNF-$\alpha$ at various times, and then IL-8 and TNF-$\alpha$mRNA expressions were assayed by Northern blot analysis. IL-$1{\beta}$ or TNF-$\alpha$-induced NF-${\kappa}B$ activation was assessed by the nuclear translocation of p65 NF-${\kappa}B$ subunit. The degradation of $I{\kappa}B{\alpha}$ and $I{\kappa}B{\beta}$ by IL-$1{\beta}$ or TNF-$\alpha$stimulation was assayed by Western blot analysis. The phosphorylation of $I{\kappa}B{\alpha}$ was evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation. The basal level of IKK $\alpha$ expression was evaluated by Western blot analysis. Results: $I{\kappa}B{\alpha}$ and $I{\kappa}B{\alpha}$ was rapidly degraded after 5 minutes of incubation with IL-$1{\beta}$ or TNF-$\alpha$ in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-${\kappa}B{\alpha}$ and the induction of IL-8 and TNF-$\alpha$ mRNA expression were observed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in these cells. In contrast, neither the changes in NF-${\kappa}B/I{\kappa}B$ pathway nor IL-8 and TNF-$\alpha$mRNA expression was induced by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in NCI-H719 cells. IL-$1{\beta}$ and TNF-$\alpha$-induced $I{\kappa}B$ phosphorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKK$\alpha$ expression was not different between cell. Conclusion : NF-${\kappa}B/I{\kappa}B$ pathway plays an important role in the expression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-${\kappa}B/I{\kappa}B$ pathway in NCI-H719 cells sæms to be due to the defect in the intracellular signal transduction pathway upstream to IKK.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.110-118
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• 2015

According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-${\kappa}B$ (TNF-${\alpha}$) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-${\alpha}$ in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-${\alpha}$, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, $PGE_2$, and TNF-${\alpha}$ in LPS-treated BV2 microglial cells by suppressing ROS and NF-${\kappa}B$. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-${\kappa}B$ signaling pathway.

• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.218-223
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• 2011

Background: We investigated whether curcumin and genistein affect the MUC5AC mucin production from human airway epithelial cells that is induced by phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). Methods: Confluent NCI-H292 cells were pretreated with each agent for 30 min and then stimulated with PMA or TNF-${\alpha}$ for 24 hours. MUC5AC mucin production was measured by an ELISA. Results: (1) Curcumin dose-dependently inhibited the production of MUC5AC mucin that was induced by PMA or TNF-${\alpha}$; (2) Genistein inhibited PMA-induced MUC5AC mucin production. However, it did not decrease TNF-${\alpha}$-induced MUC5AC mucin production. Conclusion: These results suggest that curcumin and genistein inhibit the production of airway mucin induced by PMA.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.89-101
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• 2004

홍채학은 대체의학의 한 분야로서 홍채 침착의 불규칙성을 주시함으로써 의학적 상태를 진단한다. 홍채학적 분류에 의한 체질은 가족력을 보이고 있으며 이는 홍채체질의 유전성을 의미한다. 강력한 면역조절자이며 전 염증성 사이토카인인 종양괴사인자(tumor necrosis factor-a, TNF-${\alpha}$)는 많은 병리적 과정에서 중요한 역할을 한다. 따라서 본 연구자는 고혈압환자에서 홍채체질과 TNF-${\alpha}$ 유전자 다형성과의 관련성을 조사하였다. 87명의 고혈압 환자와 79명의 정상인을 홍채체질에 따라 분류하였으며 이들의 TNF-${\alpha}$ 유전자형을 분석하였다. 결과적으로 정상인에 비하여 TNF-${\alpha}$ GA 이형접합체의 빈도가 고혈압 환자군에서 감소하였다. 이 같은 결과는 TNF-${\alpha}$ 다형성이 고혈압에 대한 저항성과 관련 있음을 의미한다. 또한 고혈압환자에서 콜레스테롤 침착체질과 심신 결합조직 허약 체질은 42.5%로서 정상인 16.5%에 비하여 현저하게 증가하였다 (P<0.001). GG TNF-${\alpha}$ 유전자형을 갖고 있는 군에서 심신 결합조직 허약체질과 콜레스테롤 침착체질의 빈도는 정상인보다 환자에서 유의하게 높았다(P<0.001). 본 연구에서 저자는 홍채체질과 고혈압사이의 관련성을 발견함과 동시에 TNF-${\alpha}$ 유전자 다형성과 고혈압, 그리고 홍채 체질과의 관련성을 최초로 입증하였다.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.1
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• pp.45-52
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• 2006

Objective: Our purpose was to investigate the relationship between the levels of IL-6 and tumor necrosis factor-${\alpha}$ in the peritoneal fluid of women with and without endometriosis and infertile women. Methods: This study is prospective and case-control study in University hospital, enrolled thirty-four women with laparoscopic findings of minimal to severe endometriosis, and thirty-seven women with no visual evidence of pelvic endometriosis and with benign gynecologic disease. IL-6 and tumor necrosis factor-${\alpha}$ levels in peritoneal fluid were determined using commercial ELISA. IL-6 and tumor necrosis factor-${\alpha}$ concentrations were compared among women with and without endometriosis, and with infertile and fertile women, and then also compared according the revised American Fertility Society classification. Results: IL-6 and tumor necrosis factor-${\alpha}$ concentrations were higher than in the peritoneal fluid of women with endometriosis than in matched normal controls. Cyclic variations in IL-6 concentrations were seen in peritoneal fluid from patients with endometriosis: the concentrations in the secretory phase were significantly higher than those in the proliferative phase. The concentrations were higher than among of infertile women than in fertile women. A significant correlation between IL-6 and tumor necrosis factor-${\alpha}$ concentrations and endometriosis stage III and IV was noted. Conclusion: Increased levels of IL-6 and tumor necrosis factor-${\alpha}$ in patients with endometriosis in the peritoneal fluid may be relate to the pathogenesis of endometriosis suggesting that partially contribute to the disturbed immune regulation observed in patients with endometriosis.

• Journal of the Korean Society of Radiology
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• v.13 no.1
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• pp.133-140
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• 2019

Triglycerides (TG) are one of the triggers of chronic inflammatory lesions in the blood vessels. In the key factors in the development of inflammatory diseases, Pro-inflammatory cytokines such as tumor necrosis factor-alpha $(TNF-){\alpha}$ and interleukin-1 beta ($IL-1{\beta}$) contribute to the development of inflammatory lesions by recruiting other immune cells in the inflamed area or causing cell necrotic death. In this study, I investigated the effect of Jurkat T lymphocytes and U937 monocytes involved in vascular inflammation development on the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ on exposure to TGs. In Jurkat cells, mRNA expression of $TNF-{\alpha}$ is increased by exposure to TGs. However, the expression levels of $TNF-{\alpha}$ and $IL-1{\beta}$ were increased by TGs in U937 cells. To investigate whether inducible nitric oxide synthase (iNOS) is involved in the increase of expression of $TNF-{\alpha}$ and $IL-1{\beta}$ by TGs, treatment of W1400 (an iNOS inhibitor) resulted in recovery of expression level both $TNF-{\alpha}$ and $IL-1{\beta}$. Based on the present study, it was confirmed that the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ in monocytes and T lymphocytes. This increased cytokines contribute to development of vascular inflammatory lesions. In addition, iNOS is involved in the increase of $TNF-{\alpha}$ and $IL-1{\beta}$ expression by TGs.

• Journal of Chest Surgery
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• v.32 no.11
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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 Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.956-961
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• 2010

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a major mediator of immuno-inflammatory activity. The purpose of this study is to investigate whether TNF-${\alpha}$ productions of mouse macrophage RAW 264.7 and human hepatocyte HepG2 are modulated by Artemisiae argi Folium water extract (AW), Lactobacillus pentosus-fermented Artemisiae argi Folium water extract (AFL), and Saccharomyces cerevisiae-fermented Artemisiae argi Folium water extract (AFS) for 3 h of incubation. Effect of AW on cell viability of HepG2 was also investigated. TNF-${\alpha}$ productions were measured by Enzyme-Linked Immnunosorbent Assay method and cell viability was measured by MTT assay. Both AFL and AFS significantly increased TNF-${\alpha}$ productions of RAW 264.7 at the concentration of 50, 100, and 200 ${\mu}g$/mL (p<0.05). Also, AFL and AFS significantly increased TNF-${\alpha}$ productions of HepG2 at the concentration of 50, 100, and 200 ${\mu}g$/mL (p<0.05). AW significantly increased TNF-${\alpha}$ production of HepG2 at the concentration of 100 and 200 ${\mu}g$/mL (p<0.05). AW did not show any cytotoxicity on HepG2 cells for 3 h. These results suggest that AFL, AFS, and AW have the immune-enhancing property related with its increasing effect on TNF-${\alpha}$ production of macrophage and hepatocyte.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.772-778
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• 2005

Purpose : Kawasaki disease(KD) is a systemic panvasculitis that causes coronary artery lesions. KD is accompanied by immunoregulatory abnormalities. Nitric oxide(NO) can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells and high levels of NO may result in coronary artery lesions. We investigated tumor necrosis factor$(TNF)-{\alpha}$ and NO production before and after intravenous immunoglobulin(IVIG) therapy to study the roles of NO and $TNF-{\alpha}$ in KD with coronary artery lesions. Methods : Serum levels of NO and $TNF-{\alpha}$ were measured in 24 patients with KD(group I, eight patients with normal coronary artery; group II, 16 patients with coronary artery lesions) and 23 controls(group III, 13 afebrile controls; group IV, 10 febrile controls). Blood samples from each subject were drawn before and after IVIG therapy and in the convalescent stage. Serum concentrations of NO and $TNF-{\alpha}$ were measured by enzyme linked immuno sorbent assay. Results : The NO levels before IVIG therapy were significantly higher in group II than in group I, group III and group IV. After IVIG therapy the levels of NO were significantly higher in group I and group II than in group III. The $TNF-{\alpha}$ levels before IVIG therapy were significantly higher in group I and group II than in group III. The serum $TNF-{\alpha}$ and NO levels were higher before IVIG therapy and decreased through the convalescent stage in KD patients. In the acute stage of KD patients with coronary artery lesions, serum NO levels significantly correlated with white blood cells (r=0.43, P<0.05). Conclusion : The serum concentration levels of $TNF-{\alpha}$ and NO were abnormally high in KD patients and NO concentrations were statistically higher in the KD patients with coronary artery abnormalities than those without coronary abnormality during the early stage of the KD. These results suggest NO may be involved in the development of coronary artery lesions.

• Journal of Korean Neurosurgical Society
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• v.57 no.2
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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.