• Korean Journal of Pharmacognosy
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• v.31 no.2
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• pp.142-148
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• 2000

The purpose of this research was to investigate effects of Samultang water extract (SMT) on cytokine production from immune cells during the late stage of pregnancy in BALB/c mice. SMT(500 mg/kg) was administered p.o. once a day for 7 days, and then thymocytes and peritoneal macrophages were separated. At the late stage of pregnant mice, the proliferation of thymocytes and the production of ${\gamma}-interferon$ in thymocytes were decreased as compared with normal group, but the production of interleukin-2 and interleukin-4 was increased. The production of tumor necrosis $factor-{\alpha}$, nitric oxide and phagocytic activity in peritoneal macrophage was increased as compared with normal group. At the late stage of pregnant mice administered with SMT, the production of interleukin-2 in thymocytes was decreased as compared with a pregnant group, but the proliferation of thymocytes, the production of ${\gamma}-interferon$ and interleukin-4 was increased. The production of tumor necrosis $factor-{\alpha}$ and nitric oxide in peritoneal macrophages were decreased as compared with a pregnant group, but phagocytic activity were increased. These results suggest that SMT has the regulative action on immune function of thymocytes and peritoneal macrophages at the late stage of pregnant mice.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.401-406
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• 2000

We investigated the effect of aqueous extract of Gleditsia sinensis thorns (Leguminosae) (GSAE) on the mast cell-dependent anaphylaxis. GSAE (0.005 to 1 ${g}/kg$) dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats. GSAE (0.1 and 1 ${g}/kg$) also significantly inhibited local anaphylaxis activated by anti-DNP IgE. When GSAE was pretreated at the same concentrations with systemic anaphylaxis, the plasma histamine levels were reduced in a dose-dependent manner. GSAE (0.001 to 1 ${m}g/ml$) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When GSAE (1 ${m}g/ml$) was added, transiently and significantly increased about fourfold compared with that of basal cells. Moreover, GSAE (0.01 and 0.1 ${m}g/ml$) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-$\alpha$ production from RPMC. These results suggest a possible use of GSAE in managing mast cell-dependent anaphylaxis.

• Biomedical Science Letters
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• v.24 no.3
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• pp.168-174
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• 2018

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, rectal bleeding and diarrhea. Gastrodia elata Blume (GE) has been used for the treatment of various diseases including neurodegenerative diseases and inflammatory disease. However, there has been no information on whether GE regulates intestinal inflammation. The aim of this study is to elucidate whether GE can protect against dextran sulfate sodium (DSS)-induced colitis in a mouse model. The colitis mice were induced by drinking water containing 5% DSS for 7 days. Body weight, colon length and clinical score were assessed to determine the effects on colitis. The levels of inflammatory cytokines, tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6 in colitis tissue were also measured. The results showed that mice administrated with DSS showed clinical signs including weight loss and reduced colon length. GE inhibited the DSS-induced loss of body weight and shortening of colon and increased Disease activity index score. Additionally, we observed that GE suppressed the levels of $TNF-{\alpha}$ and IL-6 in DSS-treated colon tissues. Collectively, these findings provide experimental evidence that GE might be a useful therapeutic agent for patients with UC.

• Molecules and Cells
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• v.45 no.4
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• pp.193-201
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• 2022

Excessive production of reactive oxygen species (ROS) is a key phenomenon in tumor necrosis factor (TNF)-α-induced cell death. However, the role of ROS in necroptosis remains mostly elusive. In this study, we show that TNF-α induces the mitochondrial accumulation of superoxide anions, not H₂O₂, in cancer cells undergoing necroptosis. TNF-α-induced mitochondrial superoxide anions production is strictly RIP3 expression-dependent. Unexpectedly, TNF-α stimulates NADPH oxidase (NOX), not mitochondrial energy metabolism, to activate superoxide production in the RIP3-positive cancer cells. In parallel, mitochondrial superoxide-metabolizing enzymes, such as manganese-superoxide dismutase (SOD2) and peroxiredoxin III, are not involved in the superoxide accumulation. Mitochondrial-targeted superoxide scavengers and a NOX inhibitor eliminate the accumulated superoxide without affecting TNF-α-induced necroptosis. Therefore, our study provides the first evidence that mitochondrial superoxide accumulation is a consequence of necroptosis.

• Journal of Periodontal and Implant Science
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• v.40 no.3
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• pp.119-124
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• 2010

Purpose: In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-$\alpha$ production in differentiated THP-1 cells, a human monocytic cell line. Methods: LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-$\alpha$ and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-$\alpha$ and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Results: Leptin enhanced P. intermedia LPS-induced TNF-$\alpha$ production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-$\alpha$ expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-$\alpha$ production was not mediated by the leptin receptor. Conclusions: The ability of leptin to enhance P. intermedia LPS-induced TNF-$\alpha$ production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

• Journal of Oriental Neuropsychiatry
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• v.10 no.1
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• pp.109-119
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• 1999

We investigated whether an aqueous extract of Chong-Myung-Tang inhibits secretion of tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$ from primary cultures of mouse astrocytes. Chong-Myung-Tang dosedependently inhibited the $TNF-{\alpha}$ secretion by astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). 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. We therefore investigated whether IL-1 mediated inhibition of $TNF-{\alpha}$ secretion from astrocytes by Chong-Myung-Tang. Treatment of Chong-Myung-Tang to astrocytes stimulated with both LPS and SP decreased IL-1 secretion. Moreover, incubation of astrocytes with IL-1 antibody abolished the synergistic cooperative effect of LPS and SP. These results suggest that Chong-Myung-Tang may inhibits $TNF-{\alpha}$ secretion by inhibiting IL-1 secretion and that Chong-Myung-Tang has a antiinflammatory activity in the central nervous system.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.177-177
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• 1996

Taurine Chloramine (Tau-Cl) inhibits production of nitric oxide(NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) in activated peritoneal macrophages, similar In that previously reported for activated RAW 264.7 cells. In addition, the effect of Tau-Cl and taurine on superoxide anion (O$\_$2/$\^$-/) Production in murine peritoneal exudate polymorphonuclear leukocytes (PMN) was examined. Tau-Cl inhibited O$\_$2/$\^$-/ production in a manner that was dose-dependent and reversible, Taurine also inhibited O$\_$2/$\^$-/ production by stimulated PMN, but at higher concentrations and to a lesser extent than Tau-Cl. The effects of taurine on O$\_$2/$\^$-/ production was attributed to the in vitro formation of Tau-Cl catalyzed by PMN associated halide-dependent myeloperoxidase. In contrast, production of NO and TNF-${\alpha}$ by activated peritoneal exudate macrophages was inhibited by Tau-Cl while taurine was without effect. These data lend support to the notion that Tau-Cl may participate ill the inflammatory responses by modulating production of inflammatory mediators.

• BMB Reports
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• v.49 no.3
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• pp.159-166
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• 2016

Several members of tumor necrosis factor receptor (TNFR) superfamily that these members activate caspase-8 from death-inducing signaling complex (DISC) in TNF ligand-receptor signal transduction have been identified. In the extrinsic pathway, apoptotic signal transduction is induced in death domain (DD) superfamily; it consists of a hexahelical bundle that contains 80 amino acids. The DD superfamily includes about 100 members that belong to four subfamilies: death domain (DD), caspase recruitment domain (CARD), pyrin domain (PYD), and death effector domain (DED). This superfamily contains key building blocks: with these blocks, multimeric complexes are formed through homotypic interactions. Furthermore, each DD-binding event occurs exclusively. The DD superfamily regulates the balance between death and survival of cells. In this study, the structures, functions, and unique features of DD superfamily members are compared with their complexes. By elucidating structural insights of DD superfamily members, we investigate the interaction mechanisms of DD domains; these domains are involved in TNF ligand-receptor signaling. These DD superfamily members play a pivotal role in the development of more specific treatments of cancer.

• Korean Journal of Medicinal Crop Science
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• v.15 no.5
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• pp.324-328
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• 2007

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $Interferon-{\gamma}\;(IFN-{\gamma})$ production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased $IFN-{\gamma}\;and\;TNF-{\alpha}$ production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.4
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• pp.329-335
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• 2018

Loss of response to anti-tumor necrosis factor (anti-TNF) agents in the treatment of inflammatory bowel disease (IBD) is a major consideration to maintain sustained response. Reversal of immunogenicity can re-establish response and increase the durability of these agents. Strategies to reverse immunogenicity include dose-intensification and/or the addition of an immunomodulator. However, there is a relative paucity of data on the efficacy of such interventions in pediatric IBD patients. Available reports have not strictly utilized homogenous mobility shift assay, which reports on anti-drug antibodies even in the presence of detectable drug, whereas prior studies have been confounded by the use of drug sensitive assays. We report four pediatric inflammatory bowel disease patients with successful reversal of immunogenicity on an anti-TNF agent using dose intensification and/or addition of an immunomodulator.