Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production11Abbreviations: CTLs, cytotoxic T lymphocytes; LAK cells, lymphokine activated killer cells; IL-2, interleukin-2; IFN-γ, interferon-gamma; TNF-α, tumor necrosis factor-α NF-κB, nuclear factor kappa B; Con A, concanavalin A; HBSS, Hanks’ balanced salt solution; DTT, dithiothreitol; PMSF, phenylmethylsulfonyl fluoride; RT-PCR, reverse transcription-polymerase chain reaction; LPS, lipopolysaccharide; and EMSA, electrophoretic mobility shift assay.

In the temporomandibular joint (TMJ) synovium, cyclo-oxygenase-2 (COX-2) expression has been believed to be directly related to joint pain and synovitis. Here we investigated the role of Nuclear Factor κB (NF-κB) in the regulation of COX-2 expression in synovial fibroblasts from human TMJ induced by tumor necrosis factor-α (TNF-α). By reverse-transcriptase/polymerase chain-reaction (RT-PCR) and Western blotting analysis, TNF-α induced a dose- and time-dependent increase in COX-2 expression. Electrophoretic mobility shift assay (EMSA) revealed that transient NF-κB activation in the COX-2 promoter was triggered by TNF-α. In parallel with transient NF-κB activation, the rapid translocation of NF-κB, particularly the p65 subunit, from the cytoplasm into the nucleus was demonstrated. Pre-treatment with pyrolidine dithiocarbamate (PDTC), one of the NF-κB inhibitors, prevented binding to the COX-2 promoter and expression of COX-2 protein in response to TNF-α. These findings indicate that activation of NF-κB is responsible for TNF-α-induced COX-2 expression in synovial fibroblasts from the TMJ.

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Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection with the tumor necrosis factor-α gene

Journal of Neurosurgery ◽

10.3171/jns.1993.78.2.0252 ◽

1993 ◽

Vol 78 (2) ◽

pp. 252-256 ◽

Cited By ~ 9

Author(s):

Takashi Tashiro ◽

Jun Yoshida ◽

Masaaki Mizuno ◽

Kenichiro Sugita

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Intrathecal Injection ◽

Malignant Gliomas ◽

Interleukin 2 ◽

Human Tumor ◽

Lak Cells ◽

Lymphokine Activated Killer Cells ◽

Tnf Α ◽

Necrosis Factor

✓ Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human tumor necrosis factor (TNF)-α gene by means of novel liposomes with a positive change on their surface. The cells secreted significant amounts of TNF-α into the culture medium and exhibited reinforcement of cytotoxicity toward a human glioma cell line (U251-SP), being three times more cytotoxic than nontransfected LAK cells. The mechanism for the reinforcement of cytotoxicity is considered to involve not only an increase in TNF-α secretion from LAK cells but also its expression on their surface. Intratumoral or intrathecal injection of LAK cells transfected with the TNF-α gene may be useful for the treatment of patients with malignant gliomas.

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Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes

Antioxidants ◽

10.3390/antiox9060530 ◽

2020 ◽

Vol 9 (6) ◽

pp. 530 ◽

Cited By ~ 1

Author(s):

Eugenie Mussard ◽

Sundy Jousselin ◽

Annabelle Cesaro ◽

Brigitte Legrain ◽

Eric Lespessailles ◽

...

Keyword(s):

Oxidative Stress ◽

Quantitative Polymerase Chain Reaction ◽

Andrographis Paniculata ◽

Ros Production ◽

Inflammatory Conditions ◽

Tnf Α ◽

Dichlorofluorescein Diacetate ◽

Polymerase Chain ◽

Factor Α ◽

Necrosis Factor

Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.

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Expression of LOXs and MMP-1, 2, 3 by ACL Fibroblasts and Synoviocytes Impact of Coculture and TNF-α

The Journal of Knee Surgery ◽

10.1055/s-0038-1641592 ◽

2018 ◽

Vol 32 (04) ◽

pp. 352-360 ◽

Cited By ~ 2

Author(s):

Chunli Wang ◽

Qingjia Chi ◽

Chunming Xu ◽

Kang Xu ◽

Yanjun Zhang ◽

...

Keyword(s):

Cruciate Ligament ◽

Cartilage Degradation ◽

Ligament Injury ◽

Tnf Α ◽

Gene And Protein Expression ◽

Polymerase Chain ◽

Anterior Cruciate ◽

Factor Α ◽

First Time ◽

Necrosis Factor

AbstractThis study aims to confirm the effects of synoviocytes (SCs) on regulating lysyl oxidases (LOXs) and matrix metalloproteinase (MMP)-1, 2, 3 in the normal and injured anterior cruciate ligament (ACL) fibroblasts response to tumor necrosis factor-α(TNF-α). The gene and protein expression levels of LOXs and MMP-1, 2, 3 in SCs cocultured ACL fibroblasts (ACLfs) induced by TNF-α and mechanical injury were analyzed by real-time polymerase chain reaction (PCR) and western bolting; the MMP-2 activity were analyzed by zymography. The results exhibited that TNF-α alone slightly downregulated the expressions of LOXs and upregulated the expression of MMP-1, 2, 3 in both normal and injured ACL fibroblasts. The decrease of LOXs and increase of MMP-1, 2, 3 in ACLfs response to TNF-α were further promoted by coculture. Taken together, these results show for the first time that the crosstalk between ACLfs and SCs could modulate the LOXs and MMP-1, 2, 3 synthesis in ACLfs in the presence of TNF-α. Accumulation of MMPs in the isolated fluid-containing space not only disrupts the balance of ACL healing, but also increases cartilage degradation and accelerates osteoarthritis (OA) in injured joint. Based on this mechanism, targeting inhibition of MMPs could provide a promising therapeutic strategy for acute ligament injury.

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Cordyceps sinensis as an Immunomodulatory Agent

The American Journal of Chinese Medicine ◽

10.1142/s0192415x96000165 ◽

1996 ◽

Vol 24 (02) ◽

pp. 111-125 ◽

Cited By ~ 94

Author(s):

Yuh-Chi Kuo ◽

Wei-Jem Tsai ◽

Ming-Shi Shiao ◽

Chieh-Fu Chen ◽

Ching-Yuang Lin

Keyword(s):

Tumor Necrosis ◽

Nk Cell ◽

Interleukin 2 ◽

Cell Activity ◽

Cordyceps Sinensis ◽

Fruiting Bodies ◽

Nk Cell Activity ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the Iymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) production on human mono-nuclear cells (HMNC) were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51) significantly inhibited the blastogenesis response (IC50 =; 71.0 ± 3.0 and 21.7 ± 2.0 μg/ml, respectively), NK cell activity (IC50 =; 25.0 ± 2.5 and 12.9 ± 5.8 μg/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC50 =; 9.6 ± 2.3 and 5.5 ± 1.6 μg/ml, respectively). TNF-α production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (IC50 =; 2.7 ± 1.0 and 12.5 ± 3.8 μg/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.

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Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains

Gut ◽

10.1136/gut.41.4.442 ◽

1997 ◽

Vol 41 (4) ◽

pp. 442-451 ◽

Cited By ~ 240

Author(s):

Y Yamaoka ◽

M Kita ◽

T Kodama ◽

N Sawai ◽

K Kashima ◽

...

Keyword(s):

Helicobacter Pylori ◽

Expression Patterns ◽

Mucosal Inflammation ◽

Enzyme Linked Immunosorbent Assay ◽

Biopsy Specimens ◽

Tnf Α ◽

Polymerase Chain ◽

H Pylori ◽

Factor Α ◽

Necrosis Factor

Background—Helicobacter pyloristrains possessing the cagA gene are thought to induce interleukin 8 (IL-8) in gastric mucosa. However, it is still unclear whether a relation exists between the cagA gene and the expression patterns of cytokines other than IL-8.Aims—To investigate the relation between the cagA gene and the production of various cytokine proteins using an enzyme linked immunosorbent assay (ELISA).Patients and methods—In 184 patients, the cagA gene was detected by polymerase chain reaction (PCR), and levels of production of IL-1β, IL-6, IL-7, IL-8, IL-10, and tumour necrosis factor α (TNF-α) in antral biopsy specimens were measured by ELISA.Results—Mucosal levels of IL-1β, IL-6, IL-8, and TNF-α were significantly higher in H pyloripositive than in H pylori negative patients. Furthermore, the mucosal levels of IL-1β and IL-8 were significantly higher in specimens infected with cagApositive strains than in those infected with cagAnegative strains. In H pylori positive patients, the mucosal level of IL-8 was closely correlated with that of IL-1β (p<0.0001), and the mucosal level of IL-6 was closely correlated with that of TNF-α (p<0.0001).Conclusion—These findings suggest that the ability to induce cytokines differs among the strains;cagA+ strains induce various kinds of cytokines and may cause severe inflammation, whereascagA− strains induce IL-8 and IL-1β only weakly and may cause only mild inflammation. However, as most patients infected with the cagA+ strains have gastritis, these strains may not be equivalent to ulcerogenic strains.

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Detection of Tumor Necrosis Factor-α mRNA Induction in Ischemic Brain Tolerance by Means of Real-Time Polymerase Chain Reaction

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200001000-00004 ◽

2000 ◽

Vol 20 (1) ◽

pp. 15-20 ◽

Cited By ~ 47

Author(s):

Xinkang Wang ◽

Xiang Li ◽

Joseph A. Erhardt ◽

Frank C. Barone ◽

Giora Z. Feuerstein

Keyword(s):

Polymerase Chain Reaction ◽

Real Time ◽

Ischemic Preconditioning ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Chain Reaction ◽

Tnf Α ◽

Polymerase Chain ◽

Factor Α ◽

Necrosis Factor

A short duration of ischemia (i.e., ischemic preconditioning) results in significant brain protection to subsequent severe ischemic insult. Because previous studies suggest that tumor necrosis factor-α (TNF-α) plays a role in both promoting ischemic damage and neuroprotection, the present work aimed to evaluate the expression of TNF-α mRNA in an established model of ischemic preconditioning using a transient 10-minute occlusion of the middle cerebral artery. Because the level of TNF-α mRNA expression in the brain was too low to be consistently detected by Northern technique, a real-time polymerase chain reaction method was applied to quantitate the absolute copy number of TNF-α transcript in rat brain after the preconditioning procedure. TNF-α mRNA was induced in the ipsilateral cortex as early as 1 hour (27 ± 1 copies of mRNA per microgram of tissue compared to 11 ± 3 copies in sham-operated samples) after preconditioning, reached a peak level at 6 hours (49 ± 10 copies of transcript, n = 4, P < 0.01), and persisted up to 2 days. These data not only demonstrate the utility of real-time polymerase chain reaction for sensitive and accurate measurement of mRNA expression in normal and injured tissues but also suggest a potential role of TNF-α in the phenomenon of ischemic preconditioning.

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Cyclosporine Ameliorates Silica-Induced Autoimmune Hepatitis in Rat Model by Altering the Expression of Toll-Like Receptor-4, Interleukin-2 and Tumor Necrosis Factor-α

Current Molecular Medicine ◽

10.2174/1566524022666220106154111 ◽

2022 ◽

Vol 22 ◽

Author(s):

Moustafa M. Mohamed ◽

Ahmed M. M. Okasha ◽

Amany H. Abdel Naiem ◽

Reham F. Mohamed ◽

Sayed F. Abdelwahab ◽

...

Keyword(s):

Autoimmune Hepatitis ◽

Interleukin 2 ◽

Hepatic Function ◽

Treated Group ◽

Control Group ◽

Toll Like Receptor ◽

Hepatic Diseases ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Background: Autoimmune hepatitis (AIH) is an inflammatory liver disease which is characterized histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by the presence of autoantibodies. Toll-like receptor (TLR)-4 is a TLR family member that, upon activation in hepatocytes, initiates a cascade of events. Interleukin-2 (IL-2) and tumour necrosis factor-α (TNF-α) are potent inflammatory cytokines secreted in AIH playing an important role in the early development of inflammation, and hepatocyte damage. Objective: This study examined cyclosporine role in AIH and tried to illustrate its actions on altered hepatic function in silica-induced AIH model. Methods: AIH was induced in Wester rats using Sodium Silicate. The rats were divided into four groups: control group, Silica-AIH group, cyclosporine-treated group, and prevention group. TLR-4, and IL-2 mRNA expression in liver tissues was tested by RT-PCR. Results: AIH was associated with up-regulation of liver enzymes, IL-2, and TLR-4 gene expression while cyclosporine significantly down-regulated the expression of both. The relative quantity of TLR-4 mRNA was 1±0, 13.57±1.91, 4±0.38, and 2±0 in the control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Also, the relative quantity of IL-2 mRNA was 1±0, 14.79±1.42, 7.07±0.96, and 3.4±0.55 in the same groups, respectively (p<0.001). Additionally, immuno-histochemical staining for TNF-α in liver sections was increased in the silica-AIH group but it was decreased in the cyclosporine-treated and prevention groups. Conclusion: This study advocates a therapeutic role of cyclosporine in treating immune-mediated hepatic diseases. Cyclosporine improves histological alterations in the liver and inhibits the production of proinflammatory cytokines.

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Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

Neural Plasticity ◽

10.1155/2021/8706400 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Jin Huang ◽

Liang Zhou ◽

Jilin Chen ◽

Tingbao Chen ◽

Bo Lei ◽

...

Keyword(s):

Oxidative Stress ◽

Sonic Hedgehog ◽

Ht22 Cells ◽

Tnf Α ◽

Mechanistic Investigation ◽

Polymerase Chain ◽

Factor Α ◽

The Relationship ◽

Type Information ◽

Necrosis Factor

Neuroinflammation plays important roles in the pathogenesis and progression of altered neurodevelopment, sensorineural hearing loss, and certain neurodegenerative diseases. Hyperoside (quercetin-3-O-β-D-galactoside) is an active compound isolated from Hypericum plants. In this study, we investigate the protective effect of hyperoside on neuroinflammation and its possible molecular mechanism. Lipopolysaccharide (LPS) and hyperoside were used to treat HT22 cells. The cell viability was measured by MTT assay. The cell apoptosis rate was measured by flow cytometry assay. The mRNA expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by quantitative reverse transcription polymerase chain reaction. The levels of oxidative stress indices superoxide dismutase (SOD), reactive oxygen species (ROS), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were measured by the kits. The expression of neurotrophic factor and the relationship among hyperoside, silent mating type information regulation 2 homolog-1 (SIRT1) and Wnt/β-catenin, and sonic hedgehog was examined by western blotting. In the LPS-induced HT22 cells, hyperoside promotes cell survival; alleviates the level of IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; and increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF. In addition, hyperoside upregulated the expression of SIRT1. Further mechanistic investigation showed that hyperoside alleviated LPS-induced inflammation, oxidative stress, and apoptosis by upregulating SIRT1 to activate Wnt/β-catenin and sonic hedgehog pathways. Taken together, our data suggested that hyperoside acts as a protector in neuroinflammation.

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