• Archives of Pharmacal Research
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• v.26 no.5
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• pp.383-388
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• 2003

Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity ($IC_{50} = 13.1 \mu$ g/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and BF-3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-$\alpha and IL-1\beta$ are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-$\alpha and IL-1\beta$ production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-$\alpha and IL-1\beta$production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production.

• 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.

• Applied Biological Chemistry
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• v.48 no.4
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• pp.315-321
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• 2005

The effects of the extracts from the bran part of pigmented rices on inflammation was evaluated by determining their inhibitory action on the histamine and ${\beta}-hexosaminidase$ release, together with inflammatory cytokine productions ($IL-1{\beta},\;TNF-{\alpha}$ and IL-6). Examination of the inhibitory effects on the histamine and ${\beta}-hexosaminidase$ release from a basophilic cell line RBL-2H3 cells and rat peritoneal mast cells (RPMC) showed that the pigmented rice extract inhibited these inflammation-mediating substances (10.19% and 110.03% inhibition in histamine and ${\beta}-hexosaminidase$ release, respectively), while normal brown rice extract rather increased their release. For RPMC, the pigmented rice extract was found to have 8 or 3-fold stronger inhibitory activity than normal brown rice toward histamine or ${\beta}-hexosaminidase$ release, respectively. Expression of $IL-1{\beta},\;TNF-{\alpha}$ and IL-6 was measured as the representative inflammatory cytokine species showed that the pigmented rice extract had a higher inhibitory activity than the normal rice counterpart. ELISA analysis for determining cytokine release demonstrated a more effective blockading ability of the pigmented rice to the release of $IL-{\beta},\;TNF-{\alpha}$ and IL-6 compared to normal rice. These results showed us the superiority of the pigmented rice bran extract not only in suppressing the release of inflammation-mediating substances such as histamine and ${\beta}-hexosaminidase$, but also in repression of the inflammatory cytokine expression.

• Journal of Korean Neurosurgical Society
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• v.42 no.3
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• pp.200-204
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• 2007

Objective : Radiation therapy is an important treatment for brain tumor. However, serious complications such as radiation necrosis can occur and it may be secondary to the expression of acute phase genes, like cytokines. In particular, inflammatory cytokines (IL-$1{\beta}$, TNF-${\alpha}$) and other immunomodulatory cytokines (TNF-${\alpha}$, TGF-${\beta}1$) might be changed after irradiation (high single dose irradiation). Although it has been reported that IL-1 level is remarkably elevated within 8 week after the irradiation to the rat brain. the change of cytokines levels at acute phase (within 24 hours) has not been reported. In the present study, we examined TNF-${\alpha}$, TGF-${\beta}1$, and IL-$1{\beta}$ levels in acute phase to clarify the early effect of cytokines on the radiation-induced brain damage. Methods : Fifty Sprague-Dawley rats were used and these were divided into irradiation group and control group. After a burr-hole trephination on the right parietal area using a drill, a single 10Gy was irradiated at the trephined site. Their forebrains were extirpated at 30 min, 2 hr, 8 hr, 12 hr and 24 hr, respectively and examined for the expression of TNF-${\alpha}$, TGF-${\beta}1$, and IL-$1{\beta}$. Results : The expression of TNF-${\alpha}$ and TGF-${\beta}1$ were decreased until 12 hr after irradiation but elevated thereafter. The expression of IL-1 was peak at 8 hr and then decreased until 12 hr but elevated after this time window. The present study indicated that expression of cytokines (TNF-${\alpha}$, TGF-${\beta}1$ and IL-$1{\beta}$) were increased at 24 hr after the irradiation to the rat brain. IL-$1{\beta}$ level, on the other hand. reached peak at 8 hr after radiation injury. Conclusion : These findings indicate that IL-1, among various cytokines, may have a more important role in the inflammatory reaction by radiation injury at acute phase and provide some clues for better understanding of the pathogenesis of radiation injury.

• The Korea Journal of Herbology
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• v.22 no.3
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• pp.93-99
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• 2007

Objective : The present study was carried out to investigate the effects of Folium Perillae (FP) on several cytokine production such as IL-1$\beta$, TNF-$\alpha$, IL-10 and TGF-$\beta$ to determine related mechanisma in Rats. Methods: So, we investigated the effects of FP on levels of several cytokines such as IL-l$\beta$, TNF-$\alpha$, IL-10 and TGF-$\beta$ in ischemic rats. Results: In this experiment, IL-10, an immune-modulatory cytckine, level was elevated by treatment with FP, but another regulatory cytokine, TGF-$\beta$1 level was not affected. On the other hand, levels of IL-l$\beta$ and TNF-$\alpha$, an inflammatory cytokines, were lowered by treatment with FP effectively. Conclusion : In conclusion, these results suggest that FP is useful to treat patient with disease related to cerebral ischemia, because FP can elevate IL-10 level, lower IL-l$\beta$ and TNF-$\alpha$ levels.

• BMB Reports
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• v.42 no.6
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• pp.338-343
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• 2009

The Wnt/$\beta$-catenin signaling pathway alters adipocyte differentiation by inhibiting adipogenic gene expression. $\beta$-catenin plays a central role in the Wnt/$\beta$-catenin signaling pathway. In this study, we revealed that tumour necrosis factor-$\alpha$ (TNF-$\alpha$), a potential negative regulator of adipocyte differentiation, inhibits porcine adipogenesis through activation of the Wnt/$\beta$-catenin signaling pathway. Under the optimal concentration of TNF-$\alpha$, the intracellular $\beta$-catenin protein was stabilized. Thus, the intracellular lipid accumulation of porcine preadipocyte was suppressed and the expression of important adipocyte marker genes, including peroxisome proliferator-activated receptor-$\gamma$ (PPAR$\gamma$) and CCAAT/enhancer binding protein-$\alpha$ (C/EBP$\alpha$), were inhibited. However, a loss of $\beta$-catenin in porcine preadipocytes enhanced the adipogenic differentiation and attenuated TNF-$\alpha$ induced anti-adipogenesis. Taken together, this study indicated that TNF-$\alpha$ inhibits adipogenesis through stabilization of $\beta$-catenin protein in porcine preadipocytes.

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.554-563
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• 2006

Background: PM is known to induce various pulmonary diseases, including asthma, cancer, fibrosis and chronic bronchitis. Despite the epidemiological evidence the pathogenesis of PM-related pulmonary diseases is unclear. Methods: This study examined the effects of PM exposure on the secretion of $TNF-{\alpha}$ and $IL-1{\beta}$ in the cultured alveolar macrophages. The cultured primary alveolar macrophages were treated with the medium, PM ($5{\sim}20{\mu}g/cm^2$), LPS (5ng/ml), and PM with LPS for 24h and 48h respectively. ELISA was used to assay the secreted $TNF-{\alpha}$ and $IL-{\beta}$ in the culture medium. Western blotting was used to identify and determine the level of proteins isolated from the culture cells. The cells cultured in the $Lab-Tek^{(R)}$ chamber slides were stained with immunocytochemical stains. Results: PM induced $TNF-{\alpha}$ and $IL-1{\beta}$ secretion in the culturing alveolar macrophages, collected from the SPF and inflammatory rats. However, the effects were only dose-dependent in the inflammatory macrophages. When the cells were co-treated with PM and LPS, there was a significant synergistic effect compared with the LPS in the both cell types. Conclusion: PM might be play an important role in the induction and/or potentiation of various lung diseases by oversecretion of $TNF-{\alpha}$ and $IL-1{\beta}$.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• 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

• The korean journal of orthodontics
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• v.25 no.6 s.53
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• pp.689-696
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• 1995

Effects of several cytokines($IL-1{\beta},\;TNF_{\alpha},\;and\;IFN_{\gamma}$) have been examined on fetal rat osteoblast-like cells. To investigate whether cytokines play direct causal roles in production of lysosomal enzyme, fetal rat osteoblast-like cells were treated with $IL-1{\beta},\;TNF_{\alpha},\;and\;IFN_{\gamma}$, respectively or combined. And acid phosphatase was determined by biochemical method. Alkaline phosphatase was assayed to determine the effects of $IL-1{\beta},\;TNF_{\alpha},\;and\;IFN_{\gamma}$ on the expression of this enzyme. And also experiment of calcified nodule formation was performed to assess the effects of cytokines on the bone-forming activity of osteoblast-like cells in vitro. Acid phosphatase activity was significantly increased by the addition of $IL-1{\beta}\;and\;TNF_{\alpha}$, whereas decreased by $IFN_{\gamma}$. However, no significant change:: in alkaline phosphatase activity was observed when the osteoblast-like cells were treated with $IL-1{\beta}\;and\;TNF_{\alpha}$. Interestingly, $IFN_{\gamma}$ showed stimulatory effect on alkaline phosphatase activity. The number of calcified nodules was decreased by treatment of cultures with 1 ng/ml $IL-1{\beta},\;20\;ng/ml\;TNF_{\alpha}$, and 500 u/ml $IFN_{\gamma}$ continuously for 21 days, while considerable number of calcified nodules were formed in control group of osteoblast-like cell in culture for 21 days. These results seem to suggest that cytokines may play crucial roles in bone remodeling through the direct action on the osteoblast-like cell.