Santonin-Related Compound 2 Inhibits the Nuclear Translocation of NF-κB Subunit p65 by Targeting Cysteine 38 in TNF-α-Induced NF-κB Signaling Pathway

2012 ◽  
Vol 76 (12) ◽  
pp. 2360-2363 ◽  
Author(s):  
Ryuichi TAMURA ◽  
Kyoko MORIMOTO ◽  
Seiya HIRANO ◽  
Liyan WANG ◽  
Ming ZHAO ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Related Compound ◽  
Nuclear Translocation ◽  
Tnf Α

scholarly journals A Novel Inhibitor of the NF-κB Signaling Pathway Encoded by the Parapoxvirus Orf Virus

2010 ◽  
Vol 84 (8) ◽  
pp. 3962-3973 ◽  
Author(s):  
D. G. Diel ◽  
G. Delhon ◽  
S. Luo ◽  
E. F. Flores ◽  
D. L. Rock
Keyword(s):  
Immune Responses ◽  
Signaling Pathway ◽  
Viral Infections ◽  
Nuclear Translocation ◽  
Orf Virus ◽  
Necrosis Factor Alpha ◽  
Iκb Kinase ◽  
Genes Expression ◽  
Tnf Α ◽  
Factor Alpha

ABSTRACT The parapoxvirus orf virus (ORFV) is a pathogen of sheep and goats that has been used as a preventive and therapeutic immunomodulatory agent in several animal species. However, the functions (genes, proteins, and mechanisms of action) evolved by ORFV to modulate and manipulate immune responses are poorly understood. Here, the novel ORFV protein ORFV024 was shown to inhibit activation of the NF-κB signaling pathway, an important modulator of early immune responses against viral infections. Infection of primary ovine cells with an ORFV024 deletion mutant virus resulted in a marked increase in expression of NF-κB-regulated chemokines and other proinflammatory host genes. Expression of ORFV024 in cell cultures significantly decreased lipopolysaccharide (LPS)- and tumor necrosis factor alpha (TNF-α)-induced NF-κB-responsive reporter gene expression. Further, ORFV024 expression decreased TNF-α-induced phosphorylation and nuclear translocation of NF-κB-p65, phosphorylation, and degradation of IκBα, and phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, indicating that ORFV024 functions by inhibiting activation of IKKs, the bottleneck for most NF-κB activating stimuli. Although ORFV024 interferes with activation of the NF-κB signaling pathway, its deletion from the OV-IA82 genome had no significant effect on disease severity, progression, and time to resolution in sheep, indicating that ORFV024 is not essential for virus virulence in the natural host. This represents the first description of a NF-κB inhibitor encoded by a parapoxvirus.

scholarly journals p85α Acts as a Novel Signal Transducer for Mediation of Cellular Apoptotic Response to UV Radiation

2007 ◽  
Vol 27 (7) ◽  
pp. 2713-2731 ◽  
Author(s):  
Lun Song ◽  
Jingxia Li ◽  
Jianping Ye ◽  
Gang Yu ◽  
Jin Ding ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Uv Radiation ◽  
Gene Transcription ◽  
Cell Apoptosis ◽  
Cellular Response ◽  
Nuclear Translocation ◽  
Site Directed Mutagenesis ◽  
Regulatory Subunit ◽  
Special Effect ◽  
Tnf Α

ABSTRACT Apoptosis is an important cellular response to UV radiation (UVR), but the corresponding mechanisms remain largely unknown. Here we report that the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI-3K) exerted a proapoptotic role in response to UVR through the induction of tumor necrosis factor alpha (TNF-α) gene expression. This special effect of p85α was unrelated to the PI-3K-dependent signaling pathway. Further evidence demonstrated that the inducible transcription factor NFAT3 was the major downstream target of p85α for the mediation of UVR-induced apoptosis and TNF-α gene transcription. p85α regulated UVR-induced NFAT3 activation by modulation of its nuclear translocation and DNA binding and the relevant transcriptional activities. Gel shift assays and site-directed mutagenesis allowed the identification of two regions in the TNF-α gene promoter that served as the NFAT3 recognition sequences. Chromatin immunoprecipitation assays further confirmed that the recruitment of NFAT3 to the endogenous TNF-α promoter was regulated by p85α upon UVR exposure. Finally, the knockdown of the NFAT3 level by its specific small interfering RNA decreased UVR-induced TNF-α gene transcription and cell apoptosis. The knockdown of endogenous p85α blocked NFAT activity and TNF-α gene transcription, as well as cell apoptosis. Thus, we demonstrated p85α-associated but PI-3K-independent cell death in response to UVR and identified a novel p85α/NFAT3/TNF-α signaling pathway for the mediation of cellular apoptotic responses under certain stress conditions such as UVR.

Rice protein hydrolysates (RPHs) inhibit the LPS-stimulated inflammatory response and phagocytosis in RAW264.7 macrophages by regulating the NF-κB signaling pathway

RSC Advances ◽  
2016 ◽  
Vol 6 (75) ◽  
pp. 71295-71304 ◽  
Author(s):  
Li Wen ◽  
Yuehua Chen ◽  
Li Zhang ◽  
Huixin Yu ◽  
Zhou Xu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Protein Hydrolysates ◽  
Rice Protein ◽  
Phagocytic Ability ◽  
Raw264.7 Macrophages ◽  
Tnf Α

Different RPH components inhibit LPS-induced NO and TNF-α production. RPHs-C-7-3 inhibits the expression of pro-inflammatory expression. RPHs-C-7-3 suppresses the LPS-stimulated phagocytic ability. RPHs-C-7-3 regulates the nuclear translocation of p65.

scholarly journals Berry Phenolic and Volatile Extracts Inhibit Pro-Inflammatory Cytokine Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB Signaling Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 871
Author(s):  
Inah Gu ◽  
Cindi Brownmiller ◽  
Nathan B. Stebbins ◽  
Andy Mauromoustakos ◽  
Luke Howard ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Complex Mixture ◽  
Limited Information ◽  
Potential Health ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Raw264.7 Macrophage ◽  
Necrosis Factor

Berries are a rich source of phytochemicals, especially phenolics well known for protective activity against many chronic diseases. Berries also contain a complex mixture of volatile compounds that are responsible for the unique aromas of berries. However, there is very limited information on the composition and potential health benefits of berry volatiles. In this study, we isolated phenolic and volatile fractions from six common berries and characterized them by HPLC/HPLC-MS and GC/GC-MS, respectively. Berry phenolic and volatile fractions were evaluated for an anti-inflammatory effect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by measuring levels of pro-inflammatory cytokines and the nuclear factor-kappa B (NF-κB) signaling pathway. Results showed that LPS-induced excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which were inhibited by berry phenolic and volatile extracts. Moreover, berry phenolic and volatile extracts reduced the nuclear translocation of NF-κB by blocking the phosphorylation of p65 and degradation of IκBα. These findings showed that berry volatiles from six berries had comparable anti-inflammatory effects to berry phenolics through the suppression of pro-inflammatory mediators and cytokines expression via NF-κB down-regulation, despite being present in the fruit at a lower concentration.

scholarly journals DAP Inhibits the TNF-α-Induced Inflammatory Response by Modulating the MAPK Signaling Pathway in Synovial Cells

2021 ◽  
Author(s):  
Jieying Wang ◽  
Nanzhen Kuang ◽  
Mao zheng ◽  
Chan Dai ◽  
Huimin Deng ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Inflammatory Factors ◽  
Control Group ◽  
Synovial Cells ◽  
Tnf Α ◽  
Model Control

Abstract Daphnetin(DAP) is extracted from Daphne odora var. marginata and contains coumarin compounds, which have a good anti-inflammatory analgesic effect. In this study, we investigated whether daphnetin can reduce the TNF-α-induced inflammatory response by inhibiting the MAPK signaling pathway in the synovial cells of CIA rats. A model of synovial cells was constructed using CIA rats induced by TNF-α. The expression of inflammatory cytokines in the synovial cells of CIA rats was observed by real-time PCR and ELISA. The expression and nuclear translocation of MAPK signaling pathway proteins were detected by Western blot and immunofluorescence assays. The results show that the mRNA and protein levels of IL-6, TGF-β, MMP-3 and MMP-13 were significantly lower than those in the culture supernatant of the model control group. The synovial cells of CIA rats induced by TNF-α exhibited decreased expression of p-p38, p-ERK1/2 and p-JNK in the nucleus. In conclusion, daphnetin can affect the activation of the MAPK signaling pathway and reduce the expression of inflammatory factors by inhibiting the MAPK signaling pathway, which plays a role in anti-rheumatic inflammation.

TNF-α in Combination with Palmitate Enhances IL-8 Production via TLR4-Dependent Signaling Pathway—Potential Relevance to Metabolic Inflammation

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1730-P
Author(s):  
RASHEED AHMAD ◽  
NADEEM AKHTER ◽  
SHIHAB P. KOCHUMON ◽  
AREEJ ABU ALROUB ◽  
REEBY S. THOMAS ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Metabolic Inflammation ◽  
Tnf Α ◽  
Dependent Signaling Pathway

MiR-18a Downregulated RORA Inhibits the Proliferation and Tumorigenesis of Glioma Through TNF-α-Mediated NF-κB Signaling Pathway

2019 ◽  
Author(s):  
Yang Jiang ◽  
Jinpeng Zhou ◽  
Junshuang Zhao ◽  
Dianqi Hou ◽  
Haiying Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tnf Α

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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