Transcriptional Regulation of the Tumor Necrosis Factor α Gene

Jongeneel, C V

doi:10.1016/s0171-2985(11)80545-0

Cited by 59 publications

(50 citation statements)

References 21 publications

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“…4E). Along with NF-kB, MAPKs have been shown to play an important role in signaling pathways that regulate proinflammatory cytokines, iNOS, and COX-2 expression in microglia cells (21,35,36). Thus, the effect of TNB on MAPKs (ERK, p38, JNK) pathways was investigated.…”

Section: Tnb Inhibited Lps-induced Nf-kb and Jnk Activationmentioning

confidence: 99%

1-O-Tigloyl-1-O-deacetyl-nimbolinin B Inhibits LPS-Stimulated Inflammatory Responses by Suppressing NF-κB and JNK Activation in Microglia Cells

et al. 2014

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Abstract. Overactivation of microglia may contribute to the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and HIV dementia. Thus, regulating microglial activation has been an important therapeutic strategy for treating neurodegenerative diseases. In this research, we compared three limonoids compounds extracted from Melia toosendan by a cell-based assay to investigate their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated microglia cells. Our study indicated that 1-O-tigloyl-1-O-deacetyl-nimbolinin B (TNB) markedly suppressed the production of nitric oxide (NO) and tumor necrosis factor (TNF)-a in LPS-stimulated microglia cells. TNB also inhibited the gene expression of inducible nitric oxide synthase (iNOS), TNF-a, cyclooxygenase (COX-2), and interleukin (IL)-1b. In addition, TNB inhibited generation of intracellular reactive oxygen species (ROS). We found that TNB significantly attenuated the nuclear translocation of NF-kB, inhibiting the activation of c-jun N-terminal kinase (JNK) in LPS-stimulated BV-2 cells. Furthermore, TNB reduced cytotoxicity of activated microglia toward HT-22 hippocampal cells in a co-culture system. Taken together, our experimental results reveal, for the first time, that TNB is a potent inhibitor of microglia-mediated inflammation, and it might be a potential candidate for the treatment of neurodegenerative diseases.

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Section: Tnb Inhibited Lps-induced Nf-kb and Jnk Activationmentioning

confidence: 99%

1-O-Tigloyl-1-O-deacetyl-nimbolinin B Inhibits LPS-Stimulated Inflammatory Responses by Suppressing NF-κB and JNK Activation in Microglia Cells

et al. 2014

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“…Several reviews have covered various aspects of TNF transcriptional regulation. 17,18 It is important to note that the first 200 bp of the promoter are highly conserved across a range of species, with the murine, bovine and porcine promoters showing approximately 80% homology with the human promoter, while further upstream there is far less conservation between species. 18 No SNPs have been identified in this proximal portion of the promoter, where they might be expected to be able to influence transcription, while those that have been reported, all occur in regions that have no clearly established functional significance.…”

Section: Functional Studies Of the Tnf Promotermentioning

confidence: 99%

“…The major source of TNF production is the monocyte/macrophage cell population, but many other cell types, including T lymphocytes and epithelial cells, also produce TNF in response to a range of stimuli. 17,18 The binding of transcription factors, often cell specific, results in the transcription of the gene. Control at this point is important to the overall levels of TNF availability, but subsequent steps also play a significant role.…”

Section: Introductionmentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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“…It is well known that the synthesis of TNF-␣ is tightly controlled at many different levels and is subject to several negative feedback mechanisms (11,31). For example, post-transcriptional regulation of TNF-␣ production is mediated by the AU-rich element located in the TNF-␣ mRNA 3Ј-untranslated region, which controls its translation and stability (32).…”

Section: Table III Effect Of Anti-tlr Mabs On the Induction Of Tnf-␣ mentioning

confidence: 99%

The Origin of the Synergistic Effect of Muramyl Dipeptide with Endotoxin and Peptidoglycan

Wolfert

Murray

Boons

et al. 2002

Journal of Biological Chemistry

136

108

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Although the basis for the high mortality rate for patients with mixed bacterial infections is likely to be multifactorial, there is evidence for a synergistic effect of muramyldipeptide (MDP) with lipopolysaccharide (LPS) on the synthesis of proinflammatory cytokines by mononuclear phagocytes. In this study, co-incubation of human Mono Mac 6 cells with MDP and either LPS or peptidoglycan (PGN) resulted in an apparent synergistic effect on tumor necrosis factor-␣ (TNF-␣) secretion. Although incubation of cells with MDP alone produced minimal TNF-␣, it caused significant expression of TNF-␣ mRNA. These findings suggest that the majority of TNF-␣ mRNA induced by MDP alone is not translated into protein. Furthermore, simultaneous incubation of cells with MDP and either LPS or PGN resulted in TNF-␣ mRNA expression that approximated the sum of the amounts expressed in response to MDP, LPS, and PGN individually. These findings indicate that the apparent synergistic effect of MDP on TNF-␣ production induced by either LPS or PGN is due to removal of a block in translation of the mRNA expressed in response to MDP. In subsequent studies, the effects of MDP alone and its effect on the production of TNF-␣ by LPS and PGN were determined to be independent of CD14, Toll-like receptor 2, and Toll-like receptor 4. These findings indicate that MDP acts through receptor(s) other than those primarily responsible for transducing the effects of LPS and PGN. Successful treatment of patients having mixed bacterial infections is likely to require interventions that address the mechanisms involved in responses induced by a variety of bacterial cell wall components.Bacteremia is a critical problem in intensive care units, accounting for high morbidity and mortality rates. The mortality rate associated with bacteremia exceeds 30% (1, 2). In a recent 12-year clinical study, Gram-positive and Gram-negative bacteria accounted for 46.9 and 31.5% of bacteremic episodes in an intensive care unit, respectively, with Gram-positive organisms being cultured from more patients (3). Further, the incidence of combined infections increased more than 4-fold over the 12-year period and was associated with a mortality rate exceeding 55%. Based on the fact that the majority of the deleterious effects of bacteremia are caused by inflammatory responses to specific bacterial components, these findings suggest that the patient's response to a mixture of Gram-positive and Gram-negative organisms may be heightened to the detriment of the patient.The two most commonly studied components of Gram-positive and Gram-negative bacterial cell walls are peptidoglycan (PGN) 1 and lipopolysaccharide (LPS), respectively. Although Gram-negative bacterial cell walls also contain PGN, its concentration is far greater in the walls of Gram-positive bacteria (4). Proinflammatory effects of these bacterial cell wall components occur both in vitro after treatment of mononuclear phagocytes and in in vivo after exposure of whole animals, with cells and animals being more sensitive to ...

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Transcriptional Regulation of the Tumor Necrosis Factor α Gene

Cited by 59 publications

References 21 publications

1-O-Tigloyl-1-O-deacetyl-nimbolinin B Inhibits LPS-Stimulated Inflammatory Responses by Suppressing NF-κB and JNK Activation in Microglia Cells

1-O-Tigloyl-1-O-deacetyl-nimbolinin B Inhibits LPS-Stimulated Inflammatory Responses by Suppressing NF-κB and JNK Activation in Microglia Cells

Is there a future for TNF promoter polymorphisms?

The Origin of the Synergistic Effect of Muramyl Dipeptide with Endotoxin and Peptidoglycan

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