• Tuberculosis and Respiratory Diseases
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• 제71권6호
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• pp.464-469
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• 2011

Adalimumab is a full human monoclonal antibody that inhibits tumor necrosis factor-alpha (TNF-${\alpha}$). This has recently been shown to be effective in the treatment of rheumatoid arthritis (RA), ankylosing spondylitis, and other conditions. Sacoidosis is known to be the target for adalimumab but we describe a patient who has developed sarcoidosis with lung involvement during adalimumab therapy for RA. A 48-year-old woman, who was treated with adalimumab for 5 months, was admitted because of chronic cough and both hilar lymphadenopathy on chest radiography. Chest computed tomography revealed the enlargement of multiple lymph nodes in the right supraclavicular, subcarinal, both hilar and right axillary area. She was diagnosed with sarcoidosis based on the biopsy of supraclavicular lymph node, skin and lung through video-associated thoracoscopic surgery, which was non-caseating epitheloid cell granuloma and excluded from a similar disease. She was treated for sarcoidosis with prednisolone and methotrexate instead of adalimumab.

• Advances in Traditional Medicine
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• 제10권1호
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• pp.7-12
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• 2010

Typha orientalis' stem (TOS) is traditionally used as an herbal medicine for difficulty in urination, galactophoritis purulenta, whooping cough, and allergic dermatitis. However, its effect in experimental models remains unknown. Here, we report the effect of TOS on the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced inflammatory cytokine production and extracellular signal-regulated kinase (ERK) activation in the human mast cell line, HMC-1. TOS inhibited PMA plus A23187-induced cytokines such as tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin (IL)-6. Maximal inhibition rate of TNF-$\alpha$ and IL-6 production by TOS (1 mg/ml) was about 44.02%, and 45.20%, respectively (P < 0.05). In addition, TOS inhibited the expression of TNF-$\alpha$ and IL-6 mRNA under the same condition. Moreover, TOS partially blocked PMA plus A23187-induced ERK phosphorylation. These results suggested TOS could inhibit the cytokine production through blocking of ERK activity.

• 동의신경정신과학회지
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• 제12권2호
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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.

• Restorative Dentistry and Endodontics
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• 제24권1호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.131-138
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• 2012

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor ${\alpha}$ (TNF${\alpha}$) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNF${\alpha}$ production in vitro and $in$ $vivo$, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNF${\alpha}$ mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP- activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNF${\alpha}$ production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The $in$ $vivo$ effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNF${\alpha}$ mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNF${\alpha}$ production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNF${\alpha}$ production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNF${\alpha}$ production by cilostazol.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3923-3927
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• 2016

Infection with the hepatitis C virus is a major public health concern which can lead to carcinoma and liver failure. It has been shown that single nucleotide polymorphisms can affect the level of gene activity of tumor necrosis factor (TNF) which has an important role, especially in viral infections which can lead to apaptosis of infected hepatocellular cells. We investigated the impact of three possible genotypes for rs1800629 or A/G single nucleotide polymorphism located downstream of $TNF{\alpha}$ gene promoter in groups of control (n=76) and chronic hepatitis C patients (n=89) focusing on the response to treatment among sensitive and resistant groups. Genomic DNA was extracted from $500{\mu}l$ prepheral whole blood and PCR and RFLP were used to amplify the region of interest and genotyping. With statistical analyzes a p-value <0.05 was considered meaningful. There was no significant difference in distribution of possible three genotypes among healthy individuals and patients (P=0.906, OR=1.194, CI=0.063-22.790). However, the frequency of G allele was higher in patients whereas A allele was more common among healthy individuals (p<0.0001). Further studies with more samples seem to be necessary.

• Advances in Traditional Medicine
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• 제4권3호
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• pp.171-178
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• 2004

Ginseng radix, the root of Panax ginseng C. A. Meyer (Araliaceae), is a medicinal plant used world-widely and has been reported to have various biological effects. To investigate the effects of Ginseng radix on HL-60 cell apoptosis, MTT assay, DNA fragmentation assay and flow cytometry were performed on HL-60 cells. Cells were treated with Ginseng radix at different concentrations $(10^{-4},\;10^{-3}\;and\;10^{-2};\;dilution\;rate)$. Ginseng radix significantly induced cells apoptosis with a time- and dose-dependent manner. To determine whether Ginseng radix-induced apoptosis is due to increase of tumor necrosis factor $(TNF-{\alpha})$ secretion, enzyme-linked immunosorbent assay was performed on HL-60 cells. Unexpectedly, Ginseng radix $(96\;{\pm}\;5\;pg/ml)$ significantly decreased the $TNF-{\alpha}$ secretion compared with control $(174\;{\pm}\;14\;pg/ml)$. Furthermore, Ginseng radix with $rIFN-{\gamma}$ synergistically increased nitric oxide production in mouse peritoneal macrophages. Taken together, our data indicate that Ginseng radix induce apoptosis on HL-60 cells without increase of $TNF-{\alpha}$ secretion and could be used for a supplementary remedy of cancer.

• 대한한방내과학회지
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• 제19권2호
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• pp.249-260
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• 1998

Ulmi radicis cortex is a herb medicine which has been used for the treatment of such allergic disease as urticaria, allergic rhinitis and athma. To assess the contribution of an aqueous extract of Ulmi radicis cortex(URC) in systemic anaphylaxis, we used compound 48/80 as a fatal anaphylaxis inducer in rats. URC inhibited anaphylactic shock 100% with a dose of 1.0 mg/g body weight (BW) 1 hr before injection of compound 48/80. URC significantly inhibited serum histamine levels induced by compound 48/80. URC (1.0 mg/g BW) also inhibited to 79.1% passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. URC dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80. Moreover, URC had a significant inhibitory effect on anti-DNP IgE-induced histamine release or tumor necrosis $factor-{\alpha}$ production from RPMC. The level of cAMP in RPMC, when URC was added, significantly increased compared with that of normal control. These results indicate that URC may possess strong antianaphylactic effect.

• Toxicological Research
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• 제27권2호
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• pp.95-102
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• 2011

The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous extracts for various respiratory disorders were evaluated on the formalin-induced paw chronic inflammation in mice after oral administration. Mice were subaponeurotically injected in the left hind paw with 0.02 ml of 3.75% formalin, then subjected to 500, 250 and 125 mg/kg of DHU001 oral administration, once a day for 10 days during which then the hind-paw thickness and volume were measured daily. The paw wet-weight, histological profiles, histomorphometrical analyses and paw tumor necrosis factor (TNF)-${\alpha}$ contents were conducted at termination. After two formalin treatments, a marked increase in the paw thickness and volume was detected in the formalin-injected control as compared with that in the intact control, plus at the time of sacrifice the paw wet-weights, paw TNF-${\alpha}$ contents were also dramatically increased with severe chronic inflammation signs at histopathological observations. However, these formalin-induced chronic inflammatory changes were dramatically decreased by treatment of dexamethasone and all three different dosages of DHU001. DHU001 has favorable effects on formalin-induced chronic inflammation mediated by TNF-${\alpha}$ suppression, and DHU001 may represent an alternative approach for the treatment of chronic inflammatory diseases.

• 동의생리병리학회지
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• 제19권5호
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• pp.1379-1385
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• 2005

Gamisaenghyeolyunbueum (GSYE) is a traditional Oriental herbal medicine prescription, which has been used for the treatment of various allergic disorders, atopic dermatitis, extravasated bleeding from skin, especially skin related disease. The author investigated the effects of GSYE on mast cell-mediated allergic inflammatory reactions. GSYE dose-dependently (0.01-1 g/kg) inhibited compound 48180-induced systemic anaphylactic shock and ear swelling response. The inhibitory effect of GSYE on the histamine release from rat peritoneal mast cells induced by compound 48f80 reveals significantly (p<0.05) at concentrations ranging from 0.01 to 1 mg/ml in a dose-dependent manner. GSYE also inhibited the passive cutaneous anaphylaxis(PCA) by oral administration at 1 g/kg. In addition, GSYE dose-dependently (0.01-1 g/kg) inhibited the phorbol 12-myristate 13-acetate(PMA) and A23187-induced tumor necrosis $factor-{\alpha}$ secretion from human mast cell line HMC-1 cells. These results indicate that GSYE may be a beneficial applicability in the allergic-related diseases.