共查询到20条相似文献,搜索用时 31 毫秒
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In this study, the role of Toll‐like receptor 2 (TLR2) in immune responses of murine peritoneal mesothelial cells against Bacteroides fragilis was investigated. Enzyme linked immunosorbent assay was used to measure cytokines and chemokines. Activation of nuclear factor κB (NF‐κB‐α) and mitogen‐activated protein kinases (MAP kinases) was investigated by western blot analysis. B. fragilis induced production of interleukin‐6, chemokine (C‐X‐C motif) ligand 1 (CXCL1) and chemokine (C‐C motif) ligand 2 (CCL2) in wild type peritoneal mesothelial cells; this was impaired in TLR2‐deficient cells. In addition, in response to B. fragilis, phosphorylation of inhibitory NF‐κB‐α and c‐Jun N‐terminal kinase mitogen‐activated protein kinase (MAPK) was induced in wild type mesothelial cells, but not in TLR2‐deficient cells,. Inhibitor assay revealed that NF‐κB and MAPKs are essential for B. fragilis‐induced production of CXCL1 and CCL2 in mesothelial cells. These findings suggest that TLR2 mediates immune responses in peritoneal mesothelial cells in response to B. fragilis. 相似文献
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Carolina Diettrich Mallet de Lima Jessica da Conceição Costa Sabrina Alves de Oliveira Lima Santos Simone Carvalho Laís de Carvalho Rodolpho Mattos Albano Mauro Martins Teixeira Maria Cristina Maciel Plotkowski Alessandra Mattos Saliba 《Cellular microbiology》2014,16(8):1244-1254
ExoU is an important virulence factor in acute Pseudomonas aeruginosa infections. Here, we unveiled the mechanisms of ExoU‐driven NF‐κB activation by using human airway cells and mice infected with P. aeruginosa strains. Several approaches showed that PAFR was crucially implicated in the activation of the canonical NF‐κB pathway. Confocal microscopy of lungs from infected mice revealed that PAFR‐dependent NF‐κB activation occurred mainly in respiratory epithelial cells, and reduced p65 nuclear translocation was detected in mice PAFR?/? or treated with the PAFR antagonist WEB 2086. Several evidences showed that ExoU‐induced NF‐κB activation regulated PAFR expression. First, ExoU increased p65 occupation of PAFR promoter, as assessed by ChIP. Second, luciferase assays in cultures transfected with different plasmid constructs revealed that ExoU promoted p65 binding to the three κB sites in PAFR promoter. Third, treatment of cell cultures with the NF‐κB inhibitor Bay 11–7082, or transfection with IκBα negative‐dominant, significantly decreased PAFR mRNA. Finally, reduction in PAFR expression was observed in mice treated with Bay 11–7082 or WEB 2086 prior to infection. Together, our data demonstrate that ExoU activates NF‐κB by PAFR signalling, which in turns enhances PAFR expression, highlighting an important mechanism of amplification of response to this P. aeruginosa toxin. 相似文献
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Hippocampal nuclear factor kappa B accounts for stress‐induced anxiety behaviors via enhancing neuronal nitric oxide synthase (nNOS)‐carboxy‐terminal PDZ ligand of nNOS‐Dexras1 coupling
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Li‐Juan Zhu Huan‐Yu Ni Rong Chen Lei Chang Hu‐Jiang Shi Dan Qiu Zhan Zhang Dan‐Lian Wu Zhao‐Chun Jiang Hong‐Liang Xin Qi‐Gang Zhou Dong‐Ya Zhu 《Journal of neurochemistry》2018,146(5):598-612
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Mikihito Kajiya Hideki Shiba Tsuyoshi Fujita Katsuhiro Takeda Yuushi Uchida Hiroyuki Kawaguchi Masae Kitagawa Takashi Takata Hidemi Kurihara 《Journal of cellular physiology》2009,221(3):696-706
Our previous studies have shown that brain‐derived neurotrophic factor (BDNF) enhances bone/cementum‐related protein gene expression through the TrkB‐c‐Raf‐ERK1/2‐Elk‐1 signaling pathway in cementoblasts, which play a critical role in the establishment of a functional periodontal ligament. To clarify how BDNF regulates survival in cementoblasts, we examined its effects on cell death induced by serum starvation in immortalized human cementoblast‐like (HCEM) cells. BDNF inhibited the death of HCEM cells. Small‐interfering RNA (siRNA) for TRKB, a high affinity receptor for BDNF, and for Bcl‐2, countered the BDNF‐induced decrease in dead cell number. In addition, LY294002, a PI3‐kinase inhibitor; SH‐6, an Akt inhibitor; and PDTC, a nuclear factor kappa B (NF‐κB) inhibitor, but not PD98059, an ERK1/2 inhibitor, abolished the protective effect of BDNF against cell death. BDNF enhanced phosphorylated Akt levels, NF‐κB activity in the nucleus, Bcl‐2 mRNA levels, and mitochondrial membrane potential. The blocking of BDNF's actions by treatment with siRNA in all cases for TRKB and Bcl‐2, LY294002, SH‐6, and PDTC suppressed the enhancement. These findings provide the first evidence that a TrkB‐PI3‐kinase‐Akt‐NF‐κB‐Bcl‐2 signaling pathway triggered by BDNF and the subsequent protective effect of BDNF on mitochondrial membrane potential are required to rescue HCEM cells from serum starvation‐induced cell death. Furthermore, the survival and increased expression of bone/cementum‐related proteins induced by BDNF in HCEM cells occur through different signaling pathways. J. Cell. Physiol. 221: 696–706, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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Integrity of IKK/NF‐κB Shields Thymic Stroma That Suppresses Susceptibility to Autoimmunity,Fungal Infection,and Carcinogenesis
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Feng Zhu Yinling Hu 《BioEssays : news and reviews in molecular, cellular and developmental biology》2018,40(4)
A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) as well as in a mouse model in which kinase‐dead Ikkα knock‐in mice develop impaired central tolerance, autoreactive T cell–mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α (IKKα) is one subunit of the IKK complex required for NF‐κB activation. IKK/NF‐κB is essential for central tolerance establishment by regulating the development of medullary thymic epithelial cells (mTECs) that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF‐κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF‐κB components, through mTEC (stroma), T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF‐κB in these diseases. 相似文献
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Syed Faisal Haider Zaidi Takeshi Yamamoto Alaa Refaat Kanwal Ahmed Hiroaki Sakurai Ikuo Saiki Takashi Kondo Khan Usmanghani Makoto Kadowaki Toshiro Sugiyama 《Helicobacter》2009,14(6):588-595
Background: Anomalous expression of activation‐induced cytidine deaminase (AID) in Helicobacter pylori‐infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)‐κB activation by H. pylori and hence, inhibition of NF‐κB pathway can downregulate the expression of AID. Curcumin, a spice‐derived polyphenol, is known for its anti‐inflammatory activity via NF‐κB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF‐κB inhibitory activity in H. pylori‐infected gastric epithelial cells. Materials and Methods: MKN‐28 or MKN‐45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co‐culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme‐linked immunosorbent assay was performed to evaluate the anti‐adhesion activity of curcumin. Real‐time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF‐κB, inhibitors of NF‐κB (IκB), and IκB kinase (IKK) complex regulation with or without curcumin. Results: The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (≤10 μmol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF‐κB activation inhibitor (SN‐50) and proteasome inhibitor (MG‐132) also downregulated the mRNA expression of AID. Moreover, curcumin (≤10 μmol/L) has suppressed H. pylori‐induced NF‐κB activation via inhibition of IKK activation and IκB degradation. Conclusion: Nonbactericidal concentrations of curcumin downregulated H. pylori‐induced AID expression in gastric epithelial cells, probably via the inhibition of NF‐κB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori‐related gastric carcinogenesis. 相似文献
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Jung Hwan Yoon Mi La Cho Yoo Jin Choi Ji Yeon Back Mi Kyung Park Suk Woo Lee Byung Joon Choi Hassan Ashktorab Duane T. Smoot Suk Woo Nam Jung Young Lee Won Sang Park 《Journal of cellular biochemistry》2013,114(8):1800-1809
Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. In this study, we examined the effect of GKN1 on the expression of inflammatory mediators, including NF‐κB, COX‐2, and cytokines in GKN1‐transfected AGS cells and shGKN1‐transfected HFE‐145 cells. Lymphocyte migration and cell viability were also analyzed after treatment with GKN1 and inflammatory cytokines in AGS cells by transwell chemotaxis and an MTT assay, respectively. In GKN1‐transfected AGS cells, we observed inactivation and reduced expression of NF‐κB and COX‐2, whereas shGKN1‐transfected HFE‐145 cells showed activation and increased expression of NF‐κB and COX‐2. GKN1 expression induced production of inflammatory cytokines including IL‐8 and ‐17A, but decreased expression of IL‐6 and ‐10. We also found IL‐17A expression in 9 (13.6%) out of 166 gastric cancer tissues and its expression was closely associated with GKN1 expression. GKN1 also acted as a chemoattractant for the migration of Jurkat T cells and peripheral B lymphocytes in the transwell assay. In addition, GKN1 significantly reduced cell viability in both AGS and HFE‐145 cells. These data suggest that the GKN1 gene may inhibit progression of gastric epithelial cells to cancer cells by regulating NF‐κB signaling pathway and cytokine expression. J. Cell. Biochem. 114: 1800–1809, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
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Xiao‐Dong Yang Bo Huang Mingxi Li Acacia Lamb Neil L Kelleher Lin‐Feng Chen 《The EMBO journal》2009,28(8):1055-1066
Proper regulation of NF‐κB activity is critical to maintain and balance the inflammatory response. Inactivation of the NF‐κB complex relies in part on the proteasome‐mediated degradation of promoter‐bound NF‐κB, but the detailed molecular mechanism initiating this process remains elusive. Here, we show that the methylation of the RelA subunit of NF‐κB has an important function in this process. Lysine methyltransferase Set9 physically associates with RelA in vitro and in vivo in response to TNF‐α stimulation. Mutational and mass spectrometric analyses reveal that RelA is monomethylated by Set9 at lysine residues 314 and 315 in vitro and in vivo. Methylation of RelA inhibits NF‐κB action by inducing the proteasome‐mediated degradation of promoter‐associated RelA. Depletion of Set9 by siRNA or mutation of the RelA methylation sites prolongs DNA binding of NF‐κB and enhances TNF‐α‐induced expression of NF‐κB target genes. Together, these findings unveil a novel mechanism by which methylation of RelA dictates the turnover of NF‐κB and controls the NF‐κB‐mediated inflammatory response. 相似文献
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This study examined the role of arachidonic acid (AA) in hypoxia‐induced production of interleukin (IL)‐6 and its related signaling pathways in mouse embryonic stem (ES) cells. Hypoxia with AA induced IL‐6 production, which was mediated by reactive oxygen species (ROS). In addition, hypoxia increased the levels of p38 mitogen‐activated protein kinases (MAPKs) and stress‐activated protein kinase/c‐jun NH2‐terminal kinase (SAPK/JNK) phosphorylation, which were blocked by antioxidant (vitamin C). Inhibition of p38 MAPK and SAPK/JNK blocked hypoxia‐ or hypoxia with AA‐induced nuclear factor‐kappa B (NF‐κB) activation. Furthermore, hypoxia‐induced increase in hypoxia‐inducible factor‐1α (HIF‐1α) expression was regulated by NF‐κB activation. Consequently, the increased HIF‐1α expression induced activation of matrix metalloproteinase (MMP)‐2 and MMP‐9. The expression of each signaling molecule stimulated an increase in IL‐6 production that was greater in hypoxic conditions with AA than with hypoxia alone. Finally, inhibition of IL‐6 production using IL‐6 antibody or soluble IL‐6 receptor attenuated the hypoxia‐induced increases in DNA synthesis of mouse ES cells. In conclusion, AA potentiates hypoxia‐induced IL‐6 production through the MAPKs, NF‐κB, and HIF‐1α pathways in mouse ES cells. J. Cell. Physiol. 222: 574–585, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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Luis A. Videla Gladys Tapia Ramón Rodrigo Paulina Pettinelli Daniela Haim Catherine Santibañez A. Verónica Araya Gladys Smok Attila Csendes Luis Gutierrez Jorge Rojas Jaime Castillo Owen Korn Fernando Maluenda Juan C. Díaz Guillermo Rencoret Jaime Poniachik 《Obesity (Silver Spring, Md.)》2009,17(5):973-979
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Cheng‐Wei Lin Shing‐Chuan Shen Chih‐Chiang Chien Liang‐Yo Yang Lin‐Ting Shia Yen‐Chou Chen 《Journal of cellular physiology》2010,225(2):472-481
An increase in MMP‐9 gene expression and enzyme activity with stimulating the migration of GBM8401 glioma cells via wound healing assay by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) was detected in glioblastoma cells GBM8401. TPA‐induced translocation of protein kinase C (PKC)α from the cytosol to membranes, and migration of GBM8401 elicited by TPA was suppressed by adding the PKCα inhibitors, GF109203X and H7. Activation of extracellular signal‐regulated kinase (ERK) and c‐Jun‐N‐terminal kinase (JNK) by TPA was identified, and TPA‐induced migration and MMP‐9 activity was significantly blocked by ERK inhibitor PD98059 and U0126, but not JNK inhibitor SP600125. Activation of NF‐κB protein p65 nuclear translocation and IκBα protein phosphorylation with increased NF‐κB‐directed luciferase activity by TPA were observed, and these were blocked by the PD98059 and IkB inhibitor BAY117082 accompanied by reducing migration and MMP‐9 activity induced by TPA in GBM8401 cells. Transfection of GBM8401 cells with PKCα siRNA specifically reduced PKCα protein expression with blocking TPA‐induced MMP‐9 activation and migration. Additionally, suppression of TPA‐induced PKCα/ERK/NK‐κB activation, migration, and MMP‐9 activation by flavonoids including kaempferol (Kae; 3,5,7,4′‐tetrahydroxyflavone), luteolin (Lut; 5,7,3′4′‐tetrahydroxyflavone), and wogonin (Wog; 5,7‐dihydroxy‐8‐methoxyflavone) was demonstrated, and structure–activity relationship (SAR) studies showed that hydroxyl (OH) groups at C4′ and C8 are critical for flavonoids' action against MMP‐9 enzyme activation and migration/invasion of glioblastoma cells elicited by TPA. Application of flavonoids to prevent the migration/invasion of glioblastoma cells through blocking PKCα/ERK/NF‐κB activation is first demonstrated herein. J. Cell. Physiol. 225: 472–481, 2010. © 2010 Wiley‐Liss, Inc. 相似文献