• Title, Summary, Keyword: Nuclear $factor-{\kappa}B$

Search Result 882, Processing Time 0.034 seconds

Decreased Neutrophil Apoptosis in Patients with Sepsis is Related to the Activation of NF-κB (패혈증 환자에서 NF-κB 활성화에 의한 호중구 아포프토시스의 억제)

  • Kwon, Sung Youn;Lee, Choon-Taek;Kim, Young Whan;Han, Sung Koo;Shim, Young-Soo;Yoo, Chul-Gyu
    • Tuberculosis and Respiratory Diseases
    • /
    • v.54 no.5
    • /
    • pp.495-509
    • /
    • 2003
  • Background : Neutrophil-mediated inflammation is usually self-limiting, because neutrophils have a remarkably short life span. Prolonged neutrophil survival, which is caused by decreased spontaneous apoptosis, leads to persistent inflammation in sepsis. Because many inflammatory cytokines, which generate signals that delay apoptosis, are regulated by nuclear factor-${\kappa}B$ transcription factor, we hypothesized that nuclear factor-${\kappa}B$ might be related to the reduced neutrophil apoptosis observed in sepsis. Methods : Neutrophils of healthy volunteers and sepsis patients were freshly isolated from venous blood. Neutrophil apoptosis was assayed with two approaches : by counting apoptotic cells under a microscope and by flow cytometry using Annexin V. The activity of nuclear factor-${\kappa}B$ was assessed by immunofluorescent staining or electrophoretic mobility shift assay. Expression of X-linked inhibitor of apoptosis was measured by western blot assay. Results : We confirmed reduced spontaneous neutrophil apoptosis in patients with sepsis. The number of apoptotic neutrophils in patients with sepsis increased to the level of that in healthy controls after cycloheximide treatment, suggesting that decreased spontaneous neutrophil apoptosis is dependent on de novo protein synthesis. In patients with sepsis, basal neutrophil nuclear factor-${\kappa}B$ was activated compared to the level in healthy controls. Moreover, a blockade of nuclear factor-${\kappa}B$ activity reversed the decreased spontaneous neutrophil apoptosis in sepsis patients. Meanwhile, X-linked inhibition of apoptosis expression, which is regulated by nuclear factor-${\kappa}B$, decreased 24 hours after incubation in healthy persons, but persisted for 24 hours in patients with sepsis. Conclusion : These observations suggest that the reduced spontaneous neutrophil apoptosis observed in patients with sepsis may be related to the induction of survival protein by nuclear factor-${\kappa}B$.

Plasma Nuclear Factor Kappa B and Serum Peroxiredoxin 3 in Early Diagnosis of Hepatocellular Carcinoma

  • Ismail, Saber;Mayah, Wael;Battia, Hassan El;Gaballah, Hanaa;Jiman-Fatani, Asif;Hamouda, Hala;Afifi, Mohamed A.;Elmashad, Nehal;Saadany, Sherif El
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.4
    • /
    • pp.1657-1663
    • /
    • 2015
  • Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-${\kappa}B$ and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-${\kappa}B$) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-${\kappa}B$ and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-${\kappa}B$) as a target for treatment of liver fibrosis and HCC must be widely evaluated.

Mangiferin inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 expression and cellular invasion by suppressing nuclear factor-κB activity

  • Dilshara, Matharage Gayani;Kang, Chang-Hee;Choi, Yung Hyun;Kim, Gi-Young
    • BMB Reports
    • /
    • v.48 no.10
    • /
    • pp.559-564
    • /
    • 2015
  • We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-$\alpha$-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-$\alpha$-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-$\alpha$ significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-$\alpha$-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-$\alpha$-induced invasion of LNCaP cells. Compared to untreated controls, TNF-$\alpha$-stimulated LNCaP cells showed a significant increase in nuclear factor-${\kappa}B$ (NF-${\kappa}B$) luciferase activity. However, mangiferin treatment markedly decreased TNF-$\alpha$-induced NF-${\kappa}B$ luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-${\kappa}B$ subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-${\kappa}B$-mediated MMP-9 expression.

Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation

  • Park, Jin Hee;Lee, Na Kyung;Lee, Soo Young
    • Molecules and Cells
    • /
    • v.40 no.10
    • /
    • pp.706-713
    • /
    • 2017
  • Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis. In the early stage, RANK signaling is mediated by recruiting adaptor molecules such as tumor necrosis factor receptorassociated factor 6 (TRAF6), which leads to the activation of mitogen-activated protein kinases (MAPKs), and the transcription factors nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 (AP-1). Activated NF-${\kappa}B$ induces the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is the key osteoclastogenesis regulator. In the intermediate stage of signaling, the co-stimulatory signal induces $Ca^{2+}$ oscillation via activated phospholipase $C{\gamma}2$ ($PLC{\gamma}2$) together with c-Fos/AP-1, wherein $Ca^{2+}$ signaling facilitates the robust production of NFATc1. In the late stage of osteoclastogenesis, NFATc1 translocates into the nucleus where it induces numerous osteoclast-specific target genes that are responsible for cell fusion and function.

Bavachin counteracts receptor activator of nuclear factor-κB-induced osteoclastogenesis though the suppression of nuclear factor-κB signaling pathway in RAW264.7 cells

  • Kim, Bok-Hee;Cho, In-A;Kang, Kyeong-Rok;Lee, Sook-Young;Jung, Seo-Yun;Kim, Jae-Sung;Kim, Su-Gwan
    • Oral Biology Research
    • /
    • v.42 no.3
    • /
    • pp.130-139
    • /
    • 2018
  • The aim of this study was to evaluate the biological effects and cellular signaling pathways associated with the anti-osteoclastogenesis effects of bavachin, a phytoestrogen, in the receptor activator of nuclear $factor-{\kappa}B$ ligand (RANKL)- treated RAW264.7 cells. The cell viability of RAW264.7 cells was not affected upon treatment with $5-20{\mu}M$ bavachin. Furthermore, osteoclastogenesis was suppressed by bavachin in a dose-dependent manner in RAW264.7 cells treated with RANKL. Tartrate-resistant acid phosphatase, matrix metalloproteinase-9, and cathepsin K, which are closely associated with osteoclastogenesis, were significantly downregulated by bavachin in the presence of RANKL. Additionally, bavachin decreased inflammatory molecules, such as nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 in RAW264.7 cells treated with RANKL. Bavachin suppressed the RANKL-induced phosphorylation of nuclear $factor-{\kappa}B$ and subsequently inhibited the translocation of nuclear $factor-{\kappa}B$ from the cytosol to the nucleus. Taken together, the obtained data suggest that bavachin may prevent the osteoclast-mediated bone destructive disorders.

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Activates Pro-Survival Signaling Pathways, Nuclear Factor-${\kappa}B$ and Extracellular Signal-Regulated Kinase 1/2 in Trophoblast Cell Line, JEG-3

  • Ka Hakhyun
    • Reproductive and Developmental Biology
    • /
    • v.29 no.2
    • /
    • pp.101-108
    • /
    • 2005
  • Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear $factor-{\kappa}B(NF-{\kappa}B)$ determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce $NF-{\kappa}B$ and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by dephosphorylating IKKβ in TNF-α-stimulated human keratinocytes

  • Cho, Young-Chang;Kim, Ba Reum;Cho, Sayeon
    • BMB Reports
    • /
    • v.50 no.11
    • /
    • pp.584-589
    • /
    • 2017
  • Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-${\alpha}$, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-${\alpha}$. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ${\kappa}B$ ($I{\kappa}B$)-kinase ${\beta}$ ($IKK{\beta}$) at Ser177/181. This dephosphorylation led to the stabilization of $I{\kappa}B{\alpha}$ and inhibition of NF-${\kappa}B$ activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-$IKK{\beta}$ and inhibiting NF-${\kappa}B$ signaling.

The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells

  • Kwon, Seung-Hwan;Ma, Shi-Xun;Hwang, Ji-Young;Ko, Yong-Hyun;Seo, Ji-Yeon;Lee, Bo-Ram;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
    • /
    • v.24 no.3
    • /
    • pp.268-282
    • /
    • 2016
  • In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

Xanthium strumarium suppresses degranulation and pro-inflammatory cytokines secretion on the mast cells (비만세포에서의 창이자의 탈과립 및 pro-inflammatory cytokines 분비량에 미치는 영향)

  • Lyu, Ji-Hyo;Yoon, Hwa-Jung;Hong, Sang-Hoon;Ko, Woo-Shin
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
    • /
    • v.21 no.3
    • /
    • pp.82-93
    • /
    • 2008
  • Objective: Previously, the methanol extracts of the semen of Xanthium strumsrium could involved anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated Raw 264,7 cells, We evaluated the anti-allergic effects of X. strumarium on rat basophilic leukemia (RBL-2H3) cells, Methodes : To investigate the effect of X. strumarium on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced RBL-2H3 cells. The effects of X. strumarium on the degranulation and the pro-inflammatory cytokines secretion and expression from RBL-2H3 cells were evaluated with $\beta$-hexosaminidase assay, ELISA, and RT-PCR analysis, In addition, we examined the effects of X. strumarium on nuclear factor (NF)-${\kappa}B$ activation and $I{\kappa}B-\alpha$ degradation using Western blot analysis. Results : X. strumarium inhibited degranulation and secretions and expressions of pro-inflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-\alpha$), interleukin (IL)-4 and cyclooxygenase (COX)-2, on stimulated RBL-2H3 cells, however, X. strumarium not affect cell viability. In stimulated RBL-2H3 cells, the protein expression level of nuclear factor-kappa B (NF-${\kappa}B$) was decreased in the nucleus by X. strumarium. In addition, X. strumarium suppressed the degradation of inhibitory protein $I{\kappa}B-{\alpha}$ protein in RBL-2H3 cells. Conclusion : These results suggest that X. strumarium inhibits the degranulation and secretion of pro-inflammatory cytokines through blockade of NF-${\kappa}B$ activation and I $I{\kappa}B-{\alpha}$ degradation.

  • PDF

Antiinflammatory Effect of Lactic Acid Bacteria: Inhibition of Cyclooxygenase-2 by Suppressing Nuclear Factor-${\kappa}B$ in Raw264.7 Macrophage Cells

  • Lee, Jeong-Min;Hwang, Kwon-Tack;Jun, Woo-Jin;Park, Chang-Soo;Lee, Myung-Yul
    • Journal of Microbiology and Biotechnology
    • /
    • v.18 no.10
    • /
    • pp.1683-1688
    • /
    • 2008
  • Lactobacillus casei 3260 (L. casei 3260) was evaluated in relation to the inflammatory response mediated by lipopolysaccharide (LPS)-induced nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and cyclooxygenase-2 (COX-2) expression in Raw264.7 macrophage cells. The treatment of Raw264.7 cells with L. casei 3260 significantly inhibited the secretion of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and prostaglandins $E_{2}\;(PGE_{2})$, followed by suppression of COX-2. To clarify the molecular mechanism, the inhibitory effect of L. casei 3260 on the NF-${\kappa}B$ signaling pathway was examined based on the luciferase reporter activity. Although the treatment of Raw264.7 cells with L. casei 3260 did not affect the transcriptional activity of NF-${\kappa}B$, it did inhibit NF-${\kappa}B$ activation, as determined by the cytosolic p65 release and degradation of I-${\kappa}B{\alpha}$. Therefore, these findings suggest that the suppression of COX-2 through inhibiting the NF-${\kappa}B$ activation by LPS may be associated with the antiinflammatory effects of L. casei 3260 on Raw264.7 cells.