Lipopolysaccharide-induced Tumor Necrosis Factor-α Promoter Activity Is Inhibitor of Nuclear Factor-κB Kinase-dependent

Swantek, Jennifer L.; Christerson, Lori B.; Cobb, Melanie H.

doi:10.1074/jbc.274.17.11667

Cited by 57 publications

(47 citation statements)

References 41 publications

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“…pCH110 constitutively expresses the lacZ gene from a simian virus 40 promoter (Pharmacia Biotech, Inc.). pDCR-ras12V, pDCR-ras12V,37G, pRSV-p65, pCMV-IKK␤KM, pCEP4-I B␣ SS/AA, pcDNA3-HA-NIK, pcDNA3myc-NIK (EE429/430AA), and pEGFP-p65 are described elsewhere (2,17,52,54,59).…”

Section: Methodsmentioning

confidence: 99%

Ral GTPases Contribute to Regulation of Cyclin D1 through Activation of NF-κB

Henry

Moskalenko

Kaur

et al. 2000

Molecular and Cellular Biology

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Section: Methodsmentioning

confidence: 99%

Ral GTPases Contribute to Regulation of Cyclin D1 through Activation of NF-κB

Henry

Moskalenko

Kaur

et al. 2000

Molecular and Cellular Biology

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“…Activation of NF-B can occur through activation of the IB kinase-2 (IKK␤), which promotes IB degradation (44), and also through phosphoinositide-3 kinase-dependent phosphorylation of the transactivation domain of p65 (45). We found that either wortmannin, a phosphoinositide-3 kinase inhibitor, or MG132, a proteasome inhibitor that blocks IB degradation (46), is able to inhibit LPS-induced AEA synthesis, which implicates NF-B activation in this process.…”

Section: Lps-treated Macrophages Elicitmentioning

confidence: 99%

Lipopolysaccharide Induces Anandamide Synthesis in Macrophages via CD14/MAPK/Phosphoinositide 3-Kinase/NF-κB Independently of Platelet-activating Factor

Liu

Bátkai

Pacher

et al. 2003

Journal of Biological Chemistry

221

185

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Macrophage-derived endocannabinoids have been implicated in endotoxin (lipopolysaccharide (LPS))-induced hypotension, but the endocannabinoid involved and the mechanism of its regulation by LPS are unknown. In RAW264.7 mouse macrophages, LPS (10 ng/ ml) increases anandamide (AEA) levels >10-fold via CD14-, NF-B-, and p44/42-dependent, platelet-activating factor-independent activation of the AEA biosynthetic enzymes, N-acyltransferase and phospholipase D. LPS also induces the AEA-degrading enzyme fatty acid amidohydrolase (FAAH), and inhibition of FAAH activity potentiates, whereas actinomycin D or cycloheximide blocks the LPS-induced increase in AEA levels and N-acyltransferase and phospholipase D activities. In contrast, cellular levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are unaffected by LPS but increased by platelet-activating factor. LPS similarly induces AEA, but not 2-AG, in mouse peritoneal macrophages where basal AEA levels are higher, and the LPS-stimulated increase in AEA is potentiated in cells from FAAH ؊/؊ as compared with FAAH ؉/؉ mice. Intravenous administration of 10 7 LPS-treated mouse macrophages to anesthetized rats elicits hypotension, which is much greater in response to FAAH ؊/؊ than FAAH ؉/؉ cells and is susceptible to inhibition by SR141716, a cannabinoid CB 1 receptor antagonist. We conclude that AEA and 2-AG synthesis are differentially regulated in macrophages, and AEA rather than 2-AG is a major contributor to LPS-induced hypotension.Anandamide (arachidonylethanolamide, AEA) 1 and 2-arachidonoylglycerol (2-AG), recently discovered endogenous ligands of cannabinoid receptors (1), are synthesized by neurons (2) as well as macrophages (3-5) in a calcium-dependent manner. The effects of AEA at the receptor are terminated by its rapid uptake through a high affinity membrane transporter (6) and subsequent intracellular degradation by fatty acid amidohydrolase (FAAH) (7). Although 2-AG is also a substrate for FAAH in vitro, it is metabolized in vivo by a monoglyceride lipase (8). AEA and 2-AG display many of the pharmacological properties of ⌬ 9 -tetrahydrocannabinol, including the ability to elicit hypotension mediated by peripheral CB 1 receptors (9, 10), and macrophage-derived endocannabinoids have been shown to contribute to the hypotension in various forms of shock (4, 5, 11).Lipopolysaccharide (LPS), an integral part of the outer membrane of Gram-negative bacteria, is a major pathogenic factor in septic shock. Macrophages are the primary target of LPS, which interacts with the CD14 protein/toll-like receptor-4 complex (12, 13) to activate multiple signaling pathways (14), which, in turn, activate a variety of transcription factors that regulate gene expression (15). LPS induces the expression of the cytokines TNF␣, interleukin-1 (IL-1), IL-6, and IL-8, which have been implicated in the pathomechanism of septic shock (12). LPS also induces the production of lipid mediators in macrophages, such as prostaglandins (16), leukotrienes (17), and platelet-activating factor (P...

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“…LPS is then transferred to the transmembrane signaling receptor toll-like receptor 4 (TLR4) and its accessory protein MD2 (8 -10). LPS stimulation of human monocytes activates several intracellular signaling pathways that include the I B kinase (IKK)-NF-B pathway (11)(12)(13)(14)(15) and three mitogen-activated protein kinase (MAPK) pathways: p42/p44 MAPK /extracellular signal-regulated kinases 1 and 2 (ERK1/2) (16 -21), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) (22), and p38 MAPK (23,24).…”

mentioning

confidence: 99%

Genetic Deletion of the Tumor Necrosis Factor Receptor p60 or p80 Sensitizes Macrophages to Lipopolysaccharide-induced Nuclear Factor-κB, Mitogen-activated Protein Kinases, and Apoptosis

Takada

Aggarwal

2003

Journal of Biological Chemistry

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Whether deletion of tumor necrosis factor (TNF) receptor 1 or 2 affects lipopolysaccharide (LPS)-mediated signaling is not understood. In this report, we used macrophages derived from wild type (wt) mice and from mice null for the type 1 receptor (p60 ؊/؊ ), the type 2 receptor (p80 ؊/؊ ), or both (p60 ؊/؊ p80 ؊/؊ ) to investigate the effect of these receptors on LPS-mediated activation of NF-B, mitogen-activated protein kinases, and apoptosis. LPS activated NF-B by 3-4-fold in wt cells but by 9 -10-fold in p60 ؊/؊ , p80 ؊/؊ , and p60 ؊/؊ p80 ؊/؊ macrophages. These results correlated with the I B␣ kinase activation, which is needed for NF-B activation. LPSinduced cyclooxygenase-2 and inducible NO synthase proteins and NO production were maximum in p60 ؊/؊ p80 ؊/؊ macrophages and minimum in wt cells. LPS activated C-Jun N-terminal kinase, p38 MAPK , and extracellular signal-regulated kinase in wt cells, but the levels were much higher in p60 ؊/؊ , p80 ؊/؊ , and p60 ؊/؊ p80 ؊/؊ cells. LPS-induced cytotoxicity, poly(ADP-ribose) polymerase cleavage, and annexin V staining were also highest in p60 ؊/؊ p80 ؊/؊ cells and lowest in wt cells. The difference in LPS signaling was unrelated to the expression of LPS receptors, CD14, or toll-like receptor 4. Overall, our studies indicate that deletion of either of the TNF receptors sensitizes the macrophages to LPS and provide evidence for cross-talk between TNF and LPS signaling.It has been known for decades that Gram-negative bacteria and their component lipopolysaccharides (LPS) 1 have antitumor properties in vivo and that these properties are mediated primarily through production of tumor necrosis factor (TNF) (1, 2). LPS or endotoxin is a glycolipid and is an integral component of the outer membrane of Gram-negative bacteria.LPS mediates a number of biologic manifestations of sepsis, including fever, hypotension, multiple organ failure, shock, and death (3). These effects of endotoxin are believed to result from an uncontrolled production of proinflammatory cytokines produced by cells of the reticuloendothelial system, particularly macrophages. LPS-dependent macrophage activation results in the release of TNF, IL-1, IL-6, IL-8, IL-10, and IL-12.LPS interacts with most cells through CD14, a 55-kDa glycosylphosphatidylinositol-anchored protein expressed on the surface of monocytes and neutrophils (4, 5). The binding of LPS to CD14 is enhanced by the LPS-binding protein present in the serum (5, 6). Mice that lack the CD14 gene show resistance to LPS-induced shock (7). LPS is then transferred to the transmembrane signaling receptor toll-like receptor 4 (TLR4) and its accessory protein MD2 (8 -10). LPS stimulation of human monocytes activates several intracellular signaling pathways that include the I B kinase (IKK)-NF-B pathway (11-15) and three mitogen-activated protein kinase (MAPK) pathways: p42/p44 MAPK /extracellular signal-regulated kinases 1 and 2 (ERK1/2) (16 -21), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) (22), and p38 MAPK (23,24).Both LPS ...

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Lipopolysaccharide-induced Tumor Necrosis Factor-α Promoter Activity Is Inhibitor of Nuclear Factor-κB Kinase-dependent

Cited by 57 publications

References 41 publications

Ral GTPases Contribute to Regulation of Cyclin D1 through Activation of NF-κB

Ral GTPases Contribute to Regulation of Cyclin D1 through Activation of NF-κB

Lipopolysaccharide Induces Anandamide Synthesis in Macrophages via CD14/MAPK/Phosphoinositide 3-Kinase/NF-κB Independently of Platelet-activating Factor

Genetic Deletion of the Tumor Necrosis Factor Receptor p60 or p80 Sensitizes Macrophages to Lipopolysaccharide-induced Nuclear Factor-κB, Mitogen-activated Protein Kinases, and Apoptosis

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