• Journal of Oriental Neuropsychiatry
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• v.12 no.2
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• pp.173-183
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• 2001

Substance P can stimulate secretion of tumor necrosis $factor-\;{\alpha}\;(TNF-\;{\alpha}\;)$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Chilbogeum can modulate cytokines secretion from primary cultures of rat astrocytes. Chilbogeum $(10\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and Substance P. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Chilbogeum $(10,\;100\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and Substance P decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and Substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in Alzheimer's disease (AD) pathology, during which they themselves may produce still more inflammatory cytokines. Chilbogeum $(10,\;100\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by CCF-STTG1 astrocytoma cells stimulated with $A\;{\beta}$ and IL-1. These results suggest that Chilbogeum may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Chilbogeum has an antiinflammatory activity in AD brain.

• Journal of Oriental Neuropsychiatry
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• v.12 no.2
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• pp.157-171
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• 2001

Astrocytes are glial cells that play a major role in the inflammation observed in Alzheimer's disease (AD). Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in AD pathology, during which they themselves may produce still more inflammatory cytokines. Substance P (SP) can stimulate secretion of tumor necrosis $factor-\;{\alpha}$ $(TNF-\;{\alpha})$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Sunghyangjungkisan- ga- pogokyoung(Sgp) can modulate cytokines secretion from primary cultures of rat astrocytes. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Sgp $(10\;to\;1000\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Neurodegenerative processes in AD are thought to be driven in part by the deposition of ${\beta}\;-amyloid\;(A\;{\beta})$, a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with $A-{\beta}-$and IL-1. These results suggest that Sgp may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Sgp has an antiinflammatory activity in AD brain

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.1
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• pp.44-51
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• 2012

Purpose: Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-${\alpha}$ promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M:F=74:37; mean age, $11.1{\pm}2.0$ yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-${\alpha}$ levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-${\alpha}$ -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-${\alpha}$ polymorphism at the -308 or the -238 loci between group I and group II + III ($p$=0.134 and $p$=0.133). The medians of HOMA-IR were significantly different between group I and group II + III ($p$=0.001), with significant difference between group II and group III ($p$=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus ($p$=0.061) or the -238 locus ($p$=0.207) in obese children. Conclusion: TNF-${\alpha}$ promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.149-161
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• 2000

Background : Residual pleural thickening (RPT) develops in about 50% of tuberculous pleurisy ($PL_{TB}$). Some reports have suggested that elevated TNF-$\alpha$ and impaired fibrinolysis could be the cause of RPT, but until now, the mechanism and predictors of RPT have not been well known. TGF-$\beta$ has been known to promote fibrogenesis and is increased in tuberculous pleural fluid (PF). $PL_{TB}$ and malignant pleurisy ($PL_{MAL}$) manifest lymphocyte-dominant exudative pleural effusion, and it has clinical implications in the differentiation of the two diseases based on the findings of pleural effusion. We performed this study to compare pleural fluid TNF-$\alpha$ TGF-$\beta$, and fibrinolytic parameters between $PL_{TB}$ and $PL_{MAL}$, and to find the predictors of RPT in $PL_{TB}$. Methods : Thirty-five $PL_{TB}$ and 14 $PL_{MAL}$ patients who were admitted to the Asan Medical Center from February 1997 to August 1999 were enrolled. All $PL_{TB}$ patients were prescribed a primary, short-course, anti-tuberculosis regimen. INF-$\alpha$ tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), plasminogen, $\alpha$2-antiplasmin, and D-dimer were measured in both PF and PB. TGF-$\beta$was measured only in PF. Clinical characteristics, TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters were compared between patients with RPT less than 2 mm and patients with more than 2 mm of the thirty patients who completed the anti-tuberculosis treatment. Results : The levels of TNF-$\alpha$ tPA, PAI-1, plasminogen, $\alpha$2-antiplasmin, and D-dimer in PF were higher than those in peripheral blood (PB) in $PL_{TB}$, whereas only plasminogen, $\alpha$2-antiplasmin, and D-dimer were higher in PF than in PB in $PL_{MAL}$. Pleural fluid TNF-$\alpha$ TGF-$\beta$, PAI-1, plasminogen, $\alpha$2-antiplasmin were increased in $PL_{TB}$ compared with $PL_{MAL}$, but these factors did not show any further advantages over ADA in differentiation between $PL_{TB}$ and $PL_{MAL}$. TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters did not show any differences between patients with RPT less than 2 mm and patients with RPT more than 2 mm. Conclusion : Our data suggest that TNF-$\alpha$, TGF-$\beta$ and fibrinolytic parameters may play some role for the development of RPT in $PL_{TB}$, but they failed to predict the occurrence of RPT in $PL_{TB}$. Also these parameters did not seem to have any advantages over ADA in differentiating between two diseases.

• Natural Product Sciences
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• v.10 no.5
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• pp.211-216
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• 2004

Citrus unshiu (Rutaceae) has long been known as an anti-inflammatory and anti-allergic agent. In the present study, the inhibitory effect of CUWE (Citus unshiu water extract) on the production of $TNF-{\alpha}$ and tryptase was examined. In addition, a possible mechanism for the inhibition of trypsin-stimulated human leukemic mast cell-1 (HMC- 1 ) activation was determined. To do so, $TNF-{\alpha}$ production from the HMC-1 cells that were stimulated by trypsin (100 nM) in the presence or absence of CUWE $(10,\;100,\;and\;100\;{\mu}g/ml)$ was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-PCR. The tryptase production was evaluated by reverse transcription-PCR. Extracellular signal-regulated kinase (ERK) activation was analyzed by Western blot. Trypsin activity was measured by using Bz-DL-Arg-p-nitroanilide (BAPNA) as substrate. Results showed that the CUWE inhibited production of both $TNF-{\alpha}$ and tryptase from the trypsin-stimulated HMC-1 in a dose-dependent manner. The CUWE a1so inhibited the ERK phosphorylation and trysin activity. These results indicate that the CUWE had an inhibitory effect on $TNF-{\alpha}$ and the tryptase productions by blocking the ERK phosphorylation and trypsin activity.

• Molecules and Cells
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• v.28 no.6
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• pp.509-513
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• 2009

Here, we show that JNK1 and JNK3 have different roles in ${\alpha}-$ or etoposide-induced apoptosis in HeLa cells. Dominant negative JNK1 inhibited $TNF-{\alpha}-$ or etoposide-induced apoptosis, while dominant negative JNK3 promoted $TNF-{\alpha}-$ or etoposide-induced apoptosis. During $TNF-{\alpha}$-induced apoptosis, JNK1 was activated in a biphasic manner, exhibiting both transient and sustained activity, whereas JNK3 was activated early and in a transient manner. The role of JNK3 activation was an anti-apoptotic effect, while the role of JNK1 activation was a pro-apoptotic effect. These results suggest that the anti-apoptotic mechanism of JNK3 in $TNF-{\alpha}$-induced apoptosis originates before the apoptotic machinery is triggered.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2003.11a
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• pp.82-83
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• 2003

To study effect of bean extracts to lessen the growth-suppressing-effect of krill meal diet, dietary krill meal with bean extracts on the performance of broiler chicks and proliferation of splenocytes and peripheral blood mononuclear cells(PBMC) and levels of circulating TNF-$\alpha$ and ovotransferrin in plasma was assayed. The krill meal with bean extracts diet lessened the growth-suppressing effect of the krill meal diet. During acute phase responce, the krill meal with bean extracts diet decreased the proliferation of splenocytes and increased the proliferation of the PBMC and reduced the circulating levels of TNF-$\alpha$ and ovotransferrin in plasma. The results Indicated that the krill meal with bean extracts diet related with the acute phase response in broiler chicks.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2637-2641
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• 2016

Tumor necrosis factor ($TNF-{\alpha}$), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of $TNF-{\alpha}$ are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on $TNF-{\alpha}$-induced apoptosis in human colon adenocarcinoma (HT-29) cells. Nimbolide from Azadirachta indica was evaluated for cytotoxicity by methyl tetrazolium 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and phase contrast microscopy. Effects on apoptotic signaling proteins were investigated using Western blot analysis. Nimbolide showed cytotoxicity against HT-29 cells that was significantly different from the control group (p<0.01), a concentration of $10{\mu}M$ significantly inducing cell death (p<0.01). In combination with $TNF-{\alpha}$, nimbolide significantly enhanced-induced cell death. In apoptotic pathway, nimbolide activated c-Jun N-terminal kinase (JNK) phosphorylation, BH3 interacting-domain death agonist (Bid) and up-regulated the death receptor 5 (DR5) level. In the combination group, nimbolide markedly sensitized $TNF-{\alpha}$-induced JNK, Bid, caspase-3 activation and the up-regulation of DR5. Our findings overall indicate that nimbolide may enhance $TNF-{\alpha}$-mediated cellular proliferation inhibition through increasing cell apoptosis of HT-29 cells by up-reglation of DR5 expression via the JNK pathway.

• Journal of the Korean Society of Physical Medicine
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• v.8 no.4
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• pp.539-547
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• 2013

PURPOSE: This study examined the effects of exercise of diverse intensities on the expression of TNF-${\alpha}$(tumor necrosis factor-${\alpha}$) in the spinal cord in osteoarthritic rats. METHODS: Over a period of four weeks, the authors applied treadmill exercise programs of diverse intensities to Sprague-Dawley rats, to which intra-articular injection of monosodium iodoacetate(MIA, $3mg/50{\mu}l$, diluted in saline) was applied to the right knee joint to induce osteoarthritis. The four-week exercise program was not carried out with the control group(CG, n=10). Exercise programs of applicable intensities were applied to the low-intensity exercise group(LEG, n=10), moderate-intensity exercise group (MEG, n=10), and high-intensity exercise group(HEG, n=10) over the four weeks. Observations were made of expression of TNF-${\alpha}$ in the spinal cord in osteoarthritic rats using western blot analysis. RESULT: there were significant differences(p<.05) in the comparison of expression of TNF-${\alpha}$ between the four groups involved. The expression of TNF-${\alpha}$ in the spinal cord, the LEG and HEG had more elevated expression significantly than the CG(p<.05). But the MEG had reduced expression significantly than the CG(p<.05). CONCLUSION: These study results suggest that moderate-intensity exercise is effective in inhibition TNF-${\alpha}$ in the spinal cord. They also indicate that in prescribing exercise to treat osteoarthritic patients, exercise of moderate intensity is most suitable to patients' chronic pain, rather than low or high intensity.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.135-142
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• 2006

Objectives : On-Bi-Tang(OB) has been prescribed Chinese traditional medicine for the treatment of inflammatory disease such as chronic renal failure. In this study, we investigated the anti-inflammatory effect of OB extract in the BV2 murine microglial cells. Methods : After the water extract of OB was treated in BV2 cells, murine microglial line, the cell viability was measured by MTT assay. The production of nitric oxide (NO) and $TNF-{\alpha}$ was determined based on Griess reagent and enzyme linked immunosorbant assay (ELISA). mRNA expression of inducible nitric oxide synthase (iNOS) and $TNF-{\alpha}$ was analyzed by RT-PCR. Results : OB extract significantly inhibited the LPS-induced production of NO and TNF-a in BV2 cells. OB extract also suppressed the mRNA expression of iNOS and $TNF-{\alpha}$ in BV2 cells activated with LPS. Conclusion : These data suggests that OB extract may have the anti-inflammatory effect through the modulation of NO production and inflammatory cytokine such as $TNF-{\alpha}$.