Nuclear factor-?B: its role in health and disease

Kumar, Ashok; Takada, Yasunari; Boriek, Aladin M.; Aggarwal, Bharat B.

doi:10.1007/s00109-004-0555-y

Cited by 876 publications

(767 citation statements)

References 187 publications

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“…Effect of PFIO on in vitro and in vivo immunostimulating activity in mouse peritoneal macrophages Macrophages can play a critical role in the innate immune response against invading pathogens (Kumar et al, 2004;Volman et al, 2008). Therefore, we investigated whether PFIO is capable of stimulating functional activation in mouse peritoneal macrophages, such as NO production, TNF-α secretion and in vivo phagocytosis.…”

Section: Resultsmentioning

confidence: 99%

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Immunostimulating Activity by Polysaccharides Isolated from Fruiting Body of Inonotus obliquus

Won

Lee

Kwon

et al. 2011

Molecules and Cells

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In this study, we investigated the immunostimulating activity of polysaccharides isolated from fruiting body of Inonotus obliquus (PFIO). Additionally, the signaling pathway of PFIO-mediated macrophage activation was investigated in RAW264.7 macrophage cells. We found that PFIO was capable of promoting NO/ROS production, TNF-α secretion and phagocytic uptake in macrophages, as well as cell proliferation, comitogenic effect and IFN-γ/IL-4 secretion in mouse splenocytes. PFIO was able to induce the phosphorylation of three MAPKs as well as the nuclear translocation of NF-κB, resulting in activation of RAW264.7 macrophages. PFIO also induced the inhibition of TNF-α secretion by anti-TLR2 mAb, consequently, PFIO might be involved in TNF-α secretion via the TLR2 receptor. In addition, our results showed that oral administration of PFIO suppressed in vivo growth of melanoma tumor in tumorbearing mice. In conclusion, our experiments presented that PFIO effectively promotes macrophage activation through the MAPK and NF-κB signaling pathways, suggesting that PFIO may potentially regulate the immune response.

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Section: Resultsmentioning

confidence: 99%

“…5B). Macrophage activation is induced by NF-κB translocation from the cytosol to the nucleus (Kumar et al, 2004). Therefore, we also investigated whether the NF-κB signaling pathway participates in macrophage activation by PFIO.…”

Section: A B C D E Fmentioning

confidence: 99%

Immunostimulating Activity by Polysaccharides Isolated from Fruiting Body of Inonotus obliquus

Won

Lee

Kwon

et al. 2011

Molecules and Cells

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“…32 This also explains the selective deficiency of IFNg production in obese and diabetes subjects upon stimulation with IL-18: the induction of IFNg by IL-18 involves mitogen-activated protein kinase 33 and signal transducer and activator of transcription 3 (STAT-3), 34 whereas production of TNF and IL-6 are nuclear factor-kB-mediated events. 35,36 The observed resistance to the effects of IL-18 may not only be important for the energy and glucose metabolism, 12 but could also explain theFalready mentionedFincreased susceptibility to infections in obese individuals and patients with diabetes. Many common infections have been shown to be more frequent in patients with diabetes, including community-acquired pneumonia, urinary tract infection and soft-tissue infection.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

et al. 2008

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Objective: Interleukin-18 (IL-18) has been recently demonstrated to improve experimental hyperphagia and insulin resistance. Paradoxically, concentrations of circulating IL-18 in obese subjects and in patients with type 2 diabetes are increased. The objective of this study is to provide an explanation for this paradox. Design: We have hypothesized that cells from obese individuals or from patients with type 2 diabetes mellitus have a diminished response to stimulation with IL-18. IL-18 responsiveness was tested by stimulating blood monocytes of obese or diabetes patients with rIL-18 or microbial components. Results: Obese individuals and patients with type 2 diabetes mellitus exhibit increased circulating concentrations of IL-18. More importantly, leukocytes isolated from obese or type 2 diabetes patients respond poorly after stimulation with IL-18, as reflected by defective interferon-g (IFNg) production. The defective response to IL-18 stimulation was accompanied by a 50% reduction in the expression of IL-18R a and b chains. In addition, cells of patients with obesity and diabetes displayed an impaired release of IFNg after challenge with bacterial or fungal pathogens, which was due to defective IL-18-mediated signaling. Conclusion: Patients with obesity or type 2 diabetes mellitus are characterized by lower responses after stimulation with IL-18. This IL-18 resistance explains the association of obesity and diabetes with high IL-18 circulating concentrations, similar to hyperinsulinemia and hyperleptinemia. IL-18 resistance may represent an important mechanism of the increased susceptibility of these patients to a number of infections.

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“…The critical component of the NF-κB signaling pathway is a multi-protein catalytic complex IKK that phosphorylates the NF-κB inhibitor, IκBα at Ser 32 and 36 [24]. Phospho-IκBα is then targeted for proteasome-dependent degradation, thus liberating NF-κB p65-p50, which enters the nucleus and mediates NF-κB-dependent transcription of more than 150 genes [25,26]. Thus, NF-κB-dependent gene expression provides a delicate balance between cell survival functions and cell death by controlling genes encoding proteins with anti-apoptotic (FLIP, c-IAP, XIAP, Bcl-xL, TRAF1, TRAF2, COX-2) and proapoptotic functions (Fas, FasL, TRAIL) [24,27,28].…”

Section: Introductionmentioning

confidence: 99%

Dual treatment with COX-2 inhibitor and sodium arsenite leads to induction of surface Fas Ligand expression and Fas-Ligand-mediated apoptosis in human melanoma cells

Ivanov¹,

Hei²

2006

Experimental Cell Research

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Most human melanomas express Fas receptor on the cell surface, and treatment with exogenous Fas Ligand (FasL) efficiently induces apoptosis of these cells. In contrast, endogenous surface expression of FasL is suppressed in Fas-positive melanomas. We report here the use of a combination of sodium arsenite, an inhibitor of NF-κB activation, and NS398, a cyclooxygenase-2 (COX-2) inhibitor, for restoration of the surface FasL expression. We observed a large increase of Fas-mediated apoptosis in Fas-positive melanomas. This was due to induction of FasL surface expression and increased susceptibility to Fas death signaling after arsenite and NS398 treatment. Furthermore, silencing COX-2 expression by specific RNAi also effectively increased surface FasL expression following arsenite treatment. Upregulation of the surface FasL levels was based on an increase in the efficiency of translocation to the cell surface and stabilization of FasL protein on the cell surface, rather than on acceleration of the FasL gene transcription. Data obtained demonstrate that the combination of arsenite with inhibitors of COX-2 may affect the target cancer cells via induction of FasL-mediated death signaling.

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Nuclear factor-?B: its role in health and disease

Cited by 876 publications

References 187 publications

Immunostimulating Activity by Polysaccharides Isolated from Fruiting Body of Inonotus obliquus

Immunostimulating Activity by Polysaccharides Isolated from Fruiting Body of Inonotus obliquus

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

Dual treatment with COX-2 inhibitor and sodium arsenite leads to induction of surface Fas Ligand expression and Fas-Ligand-mediated apoptosis in human melanoma cells

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