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Cytokine Tumour Necrosis Factor (cytokine + tumour_necrosis_factor)
Kinds of Cytokine Tumour Necrosis Factor Selected AbstractsOnco-miR-155 targets SHIP1 to promote TNF,-dependent growth of B cell lymphomasEMBO MOLECULAR MEDICINE, Issue 5 2009Irene M. Pedersen Abstract Non-coding microRNAs (miRs) are a vital component of post-transcriptional modulation of protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR expression and the identity of the affected transcripts remain poorly understood. Here we identify the inositol phosphatase SHIP1 as a bonafide target of the oncogenic miR-155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels of miR-155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by the pro-inflammatory cytokine tumour necrosis factor , (TNF,). Anti-TNF, regimen such as eternacept or infliximab were sufficient to reduce miR-155 levels and restored SHIP1 expression in DLBCL cells with an accompanying reduction in cell proliferation. Furthermore, we observed a substantial decrease in tumour burden in DLBCL xenografts in response to eternacept. These findings strongly support the concept that cytokine-regulated miRs can function as a crucial link between inflammation and cancer, and illustrate the feasibility of anti-TNF, therapy as a novel and immediately accessible (co)treatment for DLBCL. [source] Association of longevity with IL-10 ,1082 G/A and TNF-,,308 G/A polymorphismsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2010O. F. Khabour Summary Cytokines are crucial for the regulation of inflammation development in humans. Many studies have shown that variations in cytokine genes might play a role in determining human longevity. This study examined the changes in the gene pool relevant to the ,308 G/A polymorphism in the promoter region of the proinflammatory cytokine tumour necrosis factor (TNF)-, gene and the ,1082 G/A polymorphism in the promoter region of anti-inflammatory cytokine interleukin (IL)-10 gene with aging and survival selection occurs in the Jordanian population. IL-10 ,1028 G/A and TNF-,,308 G/A were genotyped in 119 randomly selected elderly subjects (41 women and 78 men) with a mean age of 90.2 years and young control subjects of 118 (46 women and 72 men) with a mean age of 31.9 years. No significant differences were found in the genotype and allele frequencies of TNF-, gene variants between the two groups (P > 0.05) while the IL-10 genotype and allele frequencies were significantly associated with longevity in men (P < 0.05) but not in women (P < 0.05). Thus, IL-10 ,1028 G/A polymorphism seems to play a role in the pathway to longevity in Jordanian men. [source] Anti-inflammatory responses and oxidative stress in Nippostrongylus brasiliensis -induced pulmonary inflammationPARASITE IMMUNOLOGY, Issue 1 2002Kathryn S. McNeil summary Migration of L3 larvae of Nippostrongylus brasiliensis through the lungs of the rat, during primary infection, was studied at 24 h, 72 h and 8 days. At 24 h p.i., there was evidence of damage to lung epithelial cells and microvasculature, with increased protein and ,-glutamyl transpeptidase in the bronchoalveolar lavage (BAL) fluid. However, there was little evidence of inflammatory cell recruitment. At 24 h p.i., there was a significant reduction in the inflammatory cytokine tumour necrosis factor ,. Superoxide (O2,·) production was also reduced, accompanied by an increase in superoxide dismutase activity. Lipid peroxidation was reduced at 24 h p.i. and L3 larvae were shown to possess high levels of glutathione compared to host lung tissue. Nitric oxide, detected as nitrite, was produced in BAL fluid, and inducible nitric oxide synthase protein was increased by 72 h p.i. There was evidence of peroxynitrite production throughout the infection period with specific protein bands nitrosylated at 75, 30 and 25 kDa. It appears that despite early evidence of lung damage, the inflammation was reduced in response to L3 larvae of N. brasiliensis. [source] Combined cell wall polysaccharide, mycotoxin and bacterial lipopolysaccharide exposure and inflammatory cytokine responsesAPMIS, Issue 7 2009LENE JOHANNESSEN Human exposure to environmental microbes occurs regularly. Microbial compounds may interact with each other to affect cellular responses. We hypothesized that interactions between microbial compounds could modulate inflammatory cytokine responses in vitro. We investigated monocyte production of the pro-inflammatory cytokine tumour necrosis factor-, (TNF-,) and the regulatory cytokine interleukin-10 (IL-10) after combined exposure to the fungal cell wall polysaccharide mannan and to the ,-glucan laminarin, the mycotoxin citrinin and bacterial lipopolysaccharide (LPS). Interactions between the cell wall microbial compounds were estimated statistically in a general linear mixed model. We found that LPS (100 ng/ml) and the used ,-glucan (up to 1000 ,g/ml) significantly interacted with each other to reduce TNF-, production. Mannan (up to 100 ,g/ml) did not interact with the ,-glucan, but interacted with LPS. IL-10 production was induced by LPS only. The mycotoxin citrinin did not induce cytokine production, but was toxic to the cells in a dose- and time-dependent manner. However, non-toxic doses of citrinin reduced LPS-induced IL-10 production while LPS-induced TNF-, production was not similarly reduced by citrinin. In conclusion, interactions between microbial compounds can modulate cellular inflammatory cytokine production and experimental investigations of one compound at a time could give misleading conclusions about these combined effects. [source] Differential immunomodulatory properties of Bifidobacterium logum strains: relevance to probiotic selection and clinical applicationsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007M. Medina Summary Modulation of host immunity is one of the proposed benefits of the consumption of probiotics. Nonetheless, comparative studies on the immunological properties that support the selection of strains of the same species for specific health benefits are limited. In this study, the ability of different strains of Bifidobacterium longum to induce cytokine production by peripheral blood mononuclear cells (PBMCs) has been evaluated. Live cells of all B. longum strains greatly stimulated regulatory cytokine interleukin (IL)-10 and proinflammatory cytokine tumour necrosis factor (TNF)-, production. Strains of the same species also induced specific cytokine patterns, suggesting that they could drive immune responses in different directions. The probiotic strain B. longum W11 stimulated strongly the production of T helper 1 (Th1) cytokines while B. longum NCIMB 8809 and BIF53 induced low levels of Th1 cytokines and high levels of IL-10. The effects of cell-surface components obtained by sonication of B. longum strains overall confirm the effects detected by stimulation of PBMCs with live cells, indicating that these components are important determinants of the immunomodulatory activity of B. longum. Genomic DNA of some strains stimulated the production of the Th1 and pro-inflammatory cytokines, interferon (IFN)-, and TNF-,, but not that of IL-10. None of the cell-free culture supernatants of the studied strains was able to induce TNF-, production, suggesting that the proinflammatory component of these strains is associated mainly with structural cell molecules. The results suggest that despite sharing certain features, some strains can perform a better functional role than others and their careful selection for therapeutic use is desirable. [source] IMPLICATIONS OF CROSS-TALK BETWEEN TUMOUR NECROSIS FACTOR AND INSULIN-LIKE GROWTH FACTOR-1 SIGNALLING IN SKELETAL MUSCLECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2008Miranda D Grounds SUMMARY 1Inflammation, particularly the pro-inflammatory cytokine tumour necrosis factor (TNF), increases necrosis of skeletal muscle. Depletion of inflammatory cells, such as neutrophils, cromolyn blockade of mast cell degranulation or pharmacological blockade of TNF reduces necrosis of dystrophic myofibres in the mdx mouse model of the lethal childhood disease Duchenne muscular dystrophy (DMD). 2Insulin-like growth factor-1 (IGF-1) is a very important cytokine for maintenance of skeletal muscle mass and the transgenic overexpression of IGF-1 within muscle cells reduces necrosis of dystrophic myofibres in mdx mice. Thus, IGF-1 usually has the opposite effect to TNF. 3Activation of TNF signalling via the c-Jun N-terminal kinase (JNK) can inhibit IGF-1 signalling by phosphorylation and conformational changes in insulin receptor substrate (IRS)-1 downstream of the IGF-1 receptor. Such silencing of IGF-1 signalling in situations where inflammatory cytokines are elevated has many implications for skeletal muscle in vivo. 4The basis for these interactions between TNF and IGF-1 is discussed with specific reference to clinical consequences for myofibre necrosis in DMD and also for the wasting (atrophy) of skeletal muscles that occurs in very old people and in cachexia associated with inflammatory disorders. [source] Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the ,2518 A,G promoter polymorphismDIABETES OBESITY & METABOLISM, Issue 5 2005B. Zietz Aim:, To investigate the association of serum levels and the ,2518 A,G promoter polymorphism of the gene for chemokine monocyte chemoattractant protein-1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, with metabolic parameters as well as insulin, leptin and the cytokines tumour necrosis factor-, (TNF-,) and interleukin-6 (IL-6) in 534 Caucasian patients with type 2 diabetes mellitus. Methods:, MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. MCP-1 genotyping was performed by RFLP analysis in a subset of 426 patients. Results:, Two hundred and thirty-one (54.2%) patients were homozygous for the wildtype allele (AA), 156 (36.6%) were heterozygous (AG) and 39 (9.2%) were homozygous for the mutated allele (GG). Allelic frequency was similar to non-diabetic populations (wildtype allele A: 0.73; mutated allele G: 0.27). MCP-1 mean concentrations and percentiles were substantially higher in non-diabetic populations but were not influenced by the genotype (AA: 662.0 ± 323.0 pg/ml; AG: 730.6 ± 491.4 pg/ml; GG: 641.2 ± 323.8 pg/ml). MCP-1 serum levels and genotypes were only marginally related to hormones (insulin and leptin) and cytokines (TNF-, and IL-6). Conclusions:, This is the first study providing MCP-1 levels, percentiles and genotype frequency in a large and representative cohort of patients with type 2 diabetes mellitus. Compared to the literature, MCP-1 levels were found to be substantially higher in patients with type 2 diabetes mellitus. In contrast, genotype frequencies were similar compared to those in non-diabetic patients and were not related to MCP-1 levels. The mechanisms behind these elevated MCP-1 serum levels in type 2 diabetes are not to be explained by simple associations with hormones, cytokines or genotypes. [source] Role of the pro-inflammatory cytokines TNF-, and IL-1, in HIV-associated dementiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2006N. A. C. H. Brabers Abstract Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages and microglia secrete neurotoxins. Two of these neurotoxins are the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin-1, (IL-1,), which are thought to play a major role in inducing neuronal death. Both TNF-, and IL-1, increase the permeability of the blood,brain barrier, through which subsequently HIV-infected monocytes can enter the brain. They both induce over-stimulation of the NMDA-receptor via several pathways, resulting in a lethal neuronal increase in Ca2+ levels. Additionally, TNF-, co-operates with several other proinflammatory mediators to enhance their toxic effects. Although most research has focused on the neurotoxic effects of TNF-, and IL-1, in HAD, there is also evidence that these cytokines can be neuroprotective. In this paper the effect of TNF-, and IL-1, on neuronal life and death in HAD is discussed. [source] Methylenedioxymethamphetamine (MDMA, ,Ecstasy'): a stressor on the immune systemIMMUNOLOGY, Issue 4 2004Thomas J. Connor Summary Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ,Ecstasy') on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin (IL)-1,, and increases production of the endogenous immunosuppressive cytokine (IL-10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T-cell function as indicated by reduced mitogen-stimulated T-cell proliferation, and a skewing of T-cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ,chemical stressor' on the immune system. Finally, the potential of MDMA-induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed. [source] Role of serum cytokines tumour necrosis factor- , and interleukin-6 in the association between body weight and periodontal infectionJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2 2009Tuomas Saxlin Abstract Aim: To study the role of serum cytokines tumour necrosis factor , (TNF- ,) and interleukin 6 (IL-6) as potential mediators in the association between body weight and periodontal infection among an adult population. Material and Methods: This study was based on a subpopulation of the Health 2000 Health Examination Survey, which included dentate non-diabetic, non-rheumatic subjects, aged between 45 and 64 years, who had never smoked and whose serum levels of TNF- , and IL-6 were analysed and whose periodontal status was clinically determined (effective n=425). The number of teeth with periodontal pockets of 4 mm or more and the number of teeth with periodontal pockets of 6 mm or more were used as outcome variables. Relative risks and 95% confidence intervals were estimated using Poisson regression models. Results: Serum IL-6, but not TNF- , associated with teeth with deepened periodontal pockets. Multivariate models showed that IL-6, but not TNF- ,, could mediate the effect of body weight on periodontium. Conclusion: In this population of non-diabetic and non-rheumatic subjects, who had never smoked, serum IL-6 was associated with periodontal infection. The results suggest that serum IL-6 could be one mediating factor that connects body weight and periodontal infection. [source] Nicotinic acetylcholine receptor activation mediates nicotine-induced enhancement of experimental periodontitisJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2009T. Breivik Background and Objective:, Smokers have an increased risk of developing periodontitis as well as showing more rapid progression and resistance to treatment of the disease, but the biological mechanisms are poorly understood. This study was designed to investigate putative biological mechanisms by which nicotine may enhance the susceptibility and thus the course of periodontitis in an animal model. Material and Methods:, Ligature-induced periodontitis was applied in periodontitis-susceptible Fischer 344 rats. The animals were either given daily intraperitoneal injections of the nicotinic acetylcholine receptor antagonist mecamylamine (1 mg/kg) 45 min before subcutaneous injections in the neck skin of nicotine (0.8 mg/kg), or treated with the same amount of saline intraperitoneally and nicotine subcutaneously, or treated with mecamylamine and saline. Control animals received intraperitoneal and subcutaneous injections of saline only. Periodontal bone loss was assessed when the ligatures had been in place for 3 wk. Two hours before decapitation, all rats received lipopolysaccharide (LPS; 100 ,g/kg, intraperitoneally) to induce a robust immune and stress response. Results:, Compared with saline/saline-treated control animals, saline/nicotine-treated rats developed significantly more periodontal bone loss, and LPS provoked a significantly smaller increase in circulating levels of the cytokines tumour necrosis factor-,, transforming growth factor-1, and interleukin-10. Mecamylamine pretreatment of nicotine-treated rats abrogated the increased periodontal bone loss and the LPS-induced decrease in tumour necrosis factor-,, but had no significant effects on the levels of transforming growth factor-1, and interleukin-10, or the stress hormone corticosterone. Conclusion:, The results indicate that nicotine enhances the susceptibility to periodontitis via nicotinic acetylcholine receptors, which may act by suppressing protective immune responses through the cholinergic anti-inflammatory pathway. [source] | ||||||||||||||||||||||