Peptide-Mediated Disruption of NFκB/NRF Interaction Inhibits IL-8 Gene Activation by IL-1 or <i>Helicobacter pylori</i>

Bartels, Myriam; Schweda, Aike Torben; Dreikhausen, Ursula; Frank, Ronald; Resch, Klaus; Beil, Winfried; Nourbakhsh, Mahtab

doi:10.4049/jimmunol.179.11.7605

Cited by 24 publications

(50 citation statements)

References 44 publications

(67 reference statements)

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“…Comparable results were obtained from three independent experiments. Important proinflammatory cytokines, such as TNF␣ or IL-1␤, as well as LPS are known to induce IL-8 expression via NFBcontaining transcription factor complexes targeting the IL-8 promoter (25)(26)(27). To our knowledge, this is the first study to demonstrate that PPAR␦ agonists lead to a concentration-dependent phosphorylation and nuclear translocation of p65 in nonstimulated endothelial cells, thereby increasing NFB DNA binding.…”

Section: Discussionmentioning

confidence: 72%

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

Meißner

Hrgović

Doll

et al. 2010

Journal of Biological Chemistry

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It is well known that IL-8 is also regulated by mRNA stability. To provide further evidence for this concept, we performed mRNA stability assays and found that PPAR␦ agonists induce the mRNA stability of IL-8. In addition, we showed that PPAR␦ agonists induce the phosphorylation of ERK1/2 and p38, which are known to be involved in the increase of mRNA stability. The inhibition of these MAPK signaling pathways resulted in a significant suppression of the induced IL-8 expression and the reduced mRNA stability. Therefore, our data provide the first evidence that PPAR␦ induces IL-8 expression in nonstimulated endothelial cells via transcriptional as well as posttranscriptional mechanisms.Peroxisome proliferator-activated receptors (PPARs) 2 are members of the nuclear receptor/ligand-activated transcription factors superfamily and consist of three different subtypes: PPAR␣, PPAR␦, and PPAR␥. The role of these receptors was originally thought to be restricted to lipid and lipoprotein metabolism, glucose homeostasis, and cellular differentiation (1, 2). PPARs are activated by natural ligands, such as eicosanoids and fatty acids. In addition, synthetic antidiabetic thiazolidinediones and lipid-lowering fibrates have been shown to act as activators of PPAR␥ and PPAR␣, respectively (3, 4). To date, PPAR␦, which is expressed in almost all tissues, is the subtype that still remains an interesting target for new pharmaceutical drugs.New evidence suggests that PPAR␦ plays a crucial role in the regulation of differentiation, cell growth, and the metabolism of lipids and glucose (5, 6). With respect to the development of novel drugs, the effects and side effects of PPAR␦ activators are therefore of great importance.In the last few years, knowledge concerning the impact of PPAR␦ in endothelial cell function has increased. showed that the PPAR␦ agonist L-165041 suppresses C-reactive protein-induced IL-6 expression (10). The expression profile of both cytokines during treatment with various PPAR␦ agonist concentrations in the endothelial quiescent status has yet to be analyzed. Nonetheless, these studies showed that PPAR␦ agonists could suppress the inflammatory processes in activated endothelial cells. The impact of PPAR agonists on the normally quiescent endothelium, however, remains to be elucidated. This could be of significant importance due to the possible broad range of applications of PPAR␦ agonists in various diseases, such as chronic inflammation, glucose metabolism, dyslipidemia, obesity, and cancer therapy, to mention only a small number of possible medical applications.During the process of inflammation, proinflammatory cytokines are produced by various cell types. IL-8 is one of these important cytokines. It is secreted at very low levels from noninduced cells, although the secretion is increased rapidly by a * This work was supported by the Wilhelm Sander Stiftung (M. M.).

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Section: Discussionmentioning

confidence: 72%

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

Meißner

Hrgović

Doll

et al. 2010

Journal of Biological Chemistry

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“…Examples include a peptide 6 S. Sengupta, C. Yang, M. L. Hegde, and S. Mitra, unpublished observations. corresponding to the interaction domain of NFRF (NF-␤-repressing factor) that inhibits NFRF-NF-␤ p65 interaction and consequent IL-8 gene activation (45), and a STAT3-derived phosphopeptide that inhibits its dimerization and transcriptional activities (46,47). Our study providing the proof of concept of inhibiting in vivo BER by disrupting complex formation could be exploited to enhance tumor cell susceptibility to drugs.…”

Section: Discussionmentioning

confidence: 83%

The C-terminal Domain (CTD) of Human DNA Glycosylase NEIL1 Is Required for Forming BERosome Repair Complex with DNA Replication Proteins at the Replicating Genome

Hegde

Dutta

Sengupta

et al. 2015

Journal of Biological Chemistry

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Background: DNA glycosylase NEIL1 initiates prereplicative repair of oxidized DNA. Results: NEIL1 forms a multiprotein complex with DNA replication proteins via its C-terminal domain (CTD), allowing recruitment at the replication fork. Isolated CTD inhibits this interaction and repair in vitro. Conclusion:The interactions of NEIL1 are necessary for prereplicative repair. Significance: The NEIL1 CTD could serve as a target for adjuvant cancer therapy.

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“…We hypothesize a common intracellular target within the pruritic infiammatory cascade. Structure alignment analysis by NCBI-BLAST, a wellestablished technique to analyse sequence homologies, showed significant molecular resemblance between lactase-phlorizin hydrolase (LPH) and NF-kappa B repressing factor (NRF) (27,28). Therefore, NRF might be a key mediator merging both pathways.…”

Section: Discussionmentioning

confidence: 99%

Lactase Deficiency: A Potential Novel Aetiological Factor in Chronic Pruritus of Unknown Origin

Grundmann¹,

Stratmann²,

Luger³

et al. 2011

Acta Derm Venerol

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Chronic pruritus, which is associated with a wide variety of underlying diseases, represents a challenge in diagnostics and treatment in dermatology and general medicine. The cause of pruritus remains unknown in up to 45% of patients. In this study, 718 patients with chronic pruritus were analysed concerning lactase deficiency, demographic data, aetiology, duration and intensity of pruritus. A total of 154 patients were tested positive for lactase deficiency and 38.3% showed a significant anti-pruritic response to a lactose-free diet (minimum 4 weeks). The best results were observed in patients with pruritus of mixed or unknown origin (n = 91; 64% response). Age, sex, localization or duration had no significant influence on the anti-pruritic effect of a lactose-free diet. Lactase deficiency might be an independent causal factor in the elicitation of chronic pruritus. Thus, screening for lactase deficiency represents a rational step in the diagnostic work-up of chronic pruritus. In case of a positive test result, a lactose-free diet offers a low-cost, efficient and specific therapy in patients with chronic pruritus.

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Peptide-Mediated Disruption of NFκB/NRF Interaction Inhibits IL-8 Gene Activation by IL-1 or Helicobacter pylori

Cited by 24 publications

References 44 publications

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

The C-terminal Domain (CTD) of Human DNA Glycosylase NEIL1 Is Required for Forming BERosome Repair Complex with DNA Replication Proteins at the Replicating Genome

Lactase Deficiency: A Potential Novel Aetiological Factor in Chronic Pruritus of Unknown Origin

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