• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.325-331
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• 2000

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ plays important roles in inflammatory responses. Some of tetrahydroisoquinoline (THI) compounds exhibited to inhibit iNOS expression in animal studies and RAW 264.7 cells, but the action of THI on inflammatory reaction was not fully investigated. In the present study, we examined a limited series of THIs (higenamine, YS-51 and THI-52) on the $TNF-{\alpha}$ mRNA expression in mouse peritoneal macrophages by Northern analysis. When thioglycollate-stimulated peritoneal macrophages were incubated with LPS (100 ng/ml), expression of $TNF-{\alpha}$ mRNA was evident and reached its maximum at 2.5 h, which was reduced concentration-dependently by treatment with THIs. When the $TNF-{\alpha}$ activity of macrophage-conditioned media was measured using a TNF-sensitive L929 fibroblast cell line, CCL 1, all THIs increased the cell viability in a concentration dependent manner. The concentrations of THIs used are not cytotoxic by itself when analysed by MTT. Furthermore, nitrite/nitrate level was significantly reduced by the presence of THIs in cells treated with $LPS+interferon-{\gamma}\;(IFN-{\gamma}).$ It is concluded, thus, that these results strongly indicated that THIs can suppress the $TNF-{\alpha}$ expression and reduce NO, which may be useful for the inflammatory disorders.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.187-199
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• 1999

Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

• 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.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.89-96
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• 2000

A human hepatoma cell line, Hep G2 cells are a reliable for the study of alcohol-induced hepatotoxicity. In this study, the author investigated the effect of an aqueous extract of Asparagus $cochinchinensis_{MERRIL}$ (Liliaceae) roots (ACAE) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. ACAE dose-dependently inhibited the EtOH-induced tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ secretion. ACAE also inhibited the EtOH and $TNF-{\alpha}-induced$ cytotoxicity. Furthermore, the author found that ACAE inhibited the $TNF-{\alpha}-induced$ apoptosis of Hep G2 cells. These results suggest that ACAE may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.

• Safety and Health at Work
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• v.1 no.1
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• pp.69-79
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• 2010

Objectives: Various cytokines induced by inhalation of coal dust may mediate inflammation and lead to tissue damage or fibrosis, such as coal workers' pneumoconiosis (CWP). Methods: To investigate the relevance of serum cytokines in CWP, the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-${\alpha}$) as CWP biomarkers in 110 retired coal miners (22 controls and 88 CWP subjects) were related to cross sectional findings and 1-year progressive changes of the pneumoconiosis. Progressive changes of CWP were evaluated by paired comparison of chest radiographs. Analysis by a receiver operating characteristic curve assessed the biomarker potential of each cytokine. Results: The mean serum IL-8 level was significantly higher in CWP compared to controls and IL-8 levels correlated with the degree of CWP. The median serum TNF-${\alpha}$ level was significantly higher in subjects with progressive CWP compared to subjects without CWP progression. The area under the ROC curve for IL-8 (0.70) and TNF-${\alpha}$ (0.72) for CWP identification and progression, respectively, indicated the biomarker potential of the two cytokines. Serum cutoff values of IL-8 and TNF-${\alpha}$ were 11.63 pg/mL(sensitivity, 69%; specificity, 64%) and 4.52 pg/mL (sensitivity, 67%; specificity, 79%), respectively. Conclusion: The results suggest that high levels of serum IL-8 are associated with the presence of CWP and those of serum TNF-${\alpha}$ are associated with the progression of CWP.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.10 no.1
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• pp.11-19
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• 2007

Purpose: Henoch-Sch$\"{o}$nlein purpura (HSP) is a systemic vasculitis involving the skin, joints, gastrointestinal tract, and kidney. Although the pathogenesis of HSP is still unclear, tumor necrosis factor (TNF-${\alpha}$) is regarded as an important cytokine contributing to the disease. The goal of this study was to determine the role of TNF-${\alpha}$ in the pathogenesis of HSP, and to evaluate the TNF-${\alpha}$ polymorphism for genetic susceptibility to HSP. Methods: From March 2004 to November 2005, 40 children with HSP and 32 healthy controls were included. Serum TNF-${\alpha}$ levels were measured using the ELISA method during the acute and convalescent phase of HSP. The genotypic and allelic frequencies of the TNF-${\alpha}$ gene polymorphisms at positions -308 and -238 were evaluated in patients and controls. Results: Serum TNF-${\alpha}$ levels were $23.17{\pm}11.31$ pg/mL in the acute phase of children with HSP and $10.56{\pm}5.59$ pg/mL in the convalescent phase (p=0.000). There was no significant correlation between the serum TNF-${\alpha}$ levels and the clinical scores of HSP (r=0.310, p=0.070). The genotypic frequency of the TNF-${\alpha}$ -308 polymorphism in children with HSP was not significantly different compared to healthy controls (GG 80%, GA 20% vs. GG 93.8%, GA 6.2%; p=0.094). The genotypic frequency of the TNF-${\alpha}$ -238 polymorphism in children with HSP was not significantly different (GG 97.5%, GA 2.5% vs. GG 93.8%, GA 6.3%; p=0.429). Conclusion: TNF-${\alpha}$ is assumed to be the main cytokine associated with the pathogenesis of HSP during the acute phase. However, the presence of TNF-${\alpha}$ gene polymorphisms at positions -308 and -238 did not distinguish children with HSP from normal controls.

• Korean Journal of Acupuncture
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• v.23 no.1
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• pp.37-44
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• 2006

Objective : To investigate the effects of Poncirus trifoliata Pharmacopuncture on lowering lipid and contents of serum tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$ and interleukin-6 (IL-6) in hyperlipidemic rats. Methods : Triglyceride, total cholesterol, $TNF-{\alpha}$, and IL-6 levels in Poncirus trifoliata Pharmacopuncture groups were compared with those in the control group. Results : Concentration of triglyceride and total cholesterol in plasma was decreased in the Poncirus trifoliata Pharmacopuncture groups. In Poncirus trifoliata Pharmacopuncre groups, plasma LDL-cholesterol showed a lower value and HDL-cholesterol showed a higher value than those of the control group. Contents of $TNF-{\alpha}$ was decreased in the Poncirus trifoliata Pharmacopuncture groups. Contents of IL-6, however, were not significantly different. Conclusions : The results suggest that Poncirus trifoliata Pharmacopuncture may have an impact on lipid metabolism to potentially prevent development of diabetes mellitus and accompanying cerebrovascular diseases.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.149-154
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• 2000

Background: Interleron-gamma(IFN-$\gamma$) and tumor necrosis factor-alpha(TNF-$\alpha$) playa critical role in protective immunity against Mycobacterium tuberculosis infection The change of IFN-$\gamma$ and TNF -$\alpha$ producing capacity in the course of antituberculous chemotherapy in patients with pulmonary tuberculosis was evaluated in this study. Method: In 29 patients with pulmonary tuberculosis, phytohemagglutinin(PHA) or purified protein derivative(PPD) stimulated production of IFN-$\gamma$ and TNF-$\alpha$ by peripheral blood mononuclear cells was quantified. Five patients were sampled before they underwent antituberculous treatment, 11 patients after 0-4 months, six after 4-completion and seven after treatment completion. Result: There was no difference in PHA- or PPD-stimulated production of IFN-$\gamma$ and TNF-$\alpha$ between each group. Conclusion: No difference in PHA- or PPD- stimulated production of IFN-$\gamma$ and TNF-$\alpha$ between two groups could be identified according to their treatment with pulmonary tuberculosis.

• The Korea Journal of Herbology
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• v.34 no.1
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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.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.77-83
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• 1996

Platelet-activating factor(PAF) is a phospholipid mediator of pulmonary inflammation, and immunologic reaction. In this study, the role of PAF on tumor necrosis factor$(TNF_{-{\alpha}})$ production by rat alveolar macrophages(AM) was examined. When PAF $(10^{-12}{\sim}10{-16}\;M)$ alone was added to AM culture, $(TNF_{-{\alpha}})$ production was not significantly increased above the resting level. In contrast, the combined addition of PAF $(10^{-6}\;M)$ and muramyl dipeptide(MDP) $(1.0\;{\mu}g\ml)$ to AM cultures markedly enhanced $(TNF_{-{\alpha}})$ production with 8.2 fold increase compared with AM culture in resting state. This potentiative effect was 313% above the sum of the separate effects of PAF and MDP. To characterize MDP effects on $(TNF_{-{\alpha}})$ production, the dose-response of AM cultured with various concentrations of MDP was tested. High level of MDP $(10\;{\mu}g\ml)$ could not significantly enhance the potentiation effect on $(TNF_{-{\alpha}})$ production compared with AM cultures with low level of MDP $(0.1\;{\mu}g\ml)$, i.e. 112.5% vs 107.8%, respectively when $10^{-10}$ M of PAF was simultaneously added to the cell culture. These data support that the potentiation of TNF. g production in AM culture is mediated by PAF rather than MDf It was also evaluated whether the similar result was obtained in silica, respirable toxic particle-treated AM culture. $(TNF_{-{\alpha}})$ production was also significantly enhanced in the PAF $(10^{-6}\;M)$ and silica $(50\;{\mu}g\ml)$-added cell cultures with 4.7 fold above the value of silica alone-stimulated cells. These results indicate that PAF can potentiate $(TNF_{-{\alpha}})$ production by MDP-or silica- stimulated AM and suggest that PAF may play a potent role in lung inflammation and disease associated with microbe and occupational dust exposures.