A Genomic and Proteomic Analysis of Activation of the Human Neutrophil by Lipopolysaccharide and Its Mediation by p38 Mitogen-activated Protein Kinase

Fessler, Michael B.; Malcolm, Kenneth C.; Duncan, Mark W.; Worthen, G. Scott

doi:10.1074/jbc.m200755200

Cited by 160 publications

(156 citation statements)

References 66 publications

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“…A variety of cytotoxic agents and proinflammatory factors, including LPS, could activate some transcription factors and increase cytosolic GSTP1-1 level, which in turn regulated the stress signaling pathways (Pinkus et al, 1995(Pinkus et al, , 1996Fessler et al, 2002;Xue et al, 2005). However, as described in the present study, GSTP1-1 had no effect on TNF-aand TRAF2-induced NF-kB activation.…”

Section: Gstp1-1 Modulates Tnf-a Signalingcontrasting

confidence: 46%

Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2–ASK1 signals

et al. 2006

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Human glutathione S-transferase P1-1 (GSTP1-1) is an ubiquitously expressed protein that plays an important role in the detoxification and xenobiotics metabolism. It has been shown that GSTP1-1 interacts with c-Jun NH 2 -terminal kinase (JNK) and suppresses its activity. Here, we report a novel function of GSTP1-1 in regulating tumor necrosis factor-a (TNF-a)-triggered signaling. The present experiments showed that GSTP1-1 physically associated with tumor necrosis factor receptor-associated factor 2 (TRAF2) in vivo and in vitro. Overexpression of GSTP1-1 inhibited TRAF2-induced activation of both JNK and p38 but not of nuclear factor-jB (NF-jB). Glutathione S-transferase P1-1 also attenuated TRAF2-enhanced apoptosis signal-regulating kinase 1 (ASK1) autophosphorylation and inhibited TRAF2-ASK1-induced cell apoptosis by suppressing the interaction of TRAF2 and ASK1. Conversely, silencing of GSTP1-1 expression through RNA interference (RNAi) resulted in increase of TNF-a-dependent TRAF2-ASK1 association followed by hyper-activation of ASK1 and JNK. A mutant GSTP1-1 lacking TRAF domain-binding motif exhibited a significant decline of capacity to bind TRAF2 and block TRAF2-ASK1 signaling compared with the wild type of GSTP1-1. Moreover, the glutathione-conjugating activity of GSTP1-1 was not involved in the regulation of TRAF2 signaling. These findings indicate that GSTP1-1 plays an important regulatory role in TNF-a-induced signaling by forming ligand-binding interactions with TRAF2, which provides a new insight for analysing the protective effects of GSTP1-1 in tumor cells.

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Section: Gstp1-1 Modulates Tnf-a Signalingcontrasting

confidence: 46%

Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2–ASK1 signals

et al. 2006

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“…In vivo expression of TSG-6/Tnfip6 has been associated with inflammatory arthritis (3,5), but the protein is produced in a variety of cells exposed to proinflammatory stimuli in vitro (2,28,29), and also in a physiologic process such as matrix formation around the cumulus cell-oocyte complex (30). In fact, the relationship between impaired cumulus cell-oocyte matrix assembly and female sterility in Tnfip6-knockout mice reveals an essential role for this protein in the formation of crosslinked HA fibers around the oocyte that is necessary for the expansion of cumulus matrix and subsequent oocyte fertilization (15).…”

Section: Discussionmentioning

confidence: 99%

Enhanced neutrophil extravasation and rapid progression of proteoglycan‐induced arthritis in TSG‐6–knockout mice

Szántó¹,

Bárdos²,

Gál³

et al. 2004

Arthritis & Rheumatism

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Objective. To gain insight into the mechanisms of the antiinflammatory effect of tumor necrosis factor ␣ (TNF␣)-induced protein 6 (Tnfip6) in arthritis, using Tnfip6-deficient animals.Methods. TNF␣-stimulated gene 6 (TSG-6) coding for Tnfip6 was disrupted. Tnfip6-deficient mice were backcrossed into proteoglycan-induced arthritis (PGIA)-susceptible BALB/c mice, and arthritis was induced by systemic immunization with cartilage proteoglycan (PG). Thioglycollate-induced sterile peritonitis was also assessed, to monitor the early events of neutrophil extravasation in wild-type and Tnfip6-deficient mice in the presence or absence of treatment with recombinant murine Tnfip6.Results. The onset of PGIA was similar, but progression and severity were significantly greater, in Tnfip6-deficient mice compared with wild-type BALB/c mice. However, this was not associated with enhanced T or B cell responses to cartilage PGs, but rather, an early and more extensive infiltration of the synovium with neutrophil leukocytes was the most prominent histopathologic feature of PGIA in Tnfip6-deficient mice. This was accompanied by elevated serum levels of interleukin-6 and amyloid A, and significantly increased activities of the enzymes plasmin, myeloperoxidase, and neutrophil elastase in the inflamed paw joints of Tnfip6-null mice, when compared with that of the wild-type littermates. Loss of control over several components of inflammation resulted in extensive and rapid cartilage degradation, bone erosion, joint ankylosis, and deformities in Tnfip6-null animals. In support of the antiinflammatory effect of Tnfip6 via the inhibition of polymorphonuclear (PMN) cell efflux, neutrophil invasion during thioglycollate-induced peritonitis was 2-fold higher in Tnfip6-deficient animals than in wild-type animals, but was dramatically suppressed by intravenous injection of recombinant murine Tnfip6.Conclusion. Tnfip6 is a multifunctional antiinflammatory protein that is produced at the site of inflammation and can be retained by the hyaluronanrich extracellular matrix. A major effect of Tnfip6 is the inhibition of the extravasation of PMN cells, predominantly neutrophils, into the site of inflammation, most likely via a CD44/hyaluronan/Tnfip6-mediated blocking mechanism.

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“…Genomic and proteomic studies were performed on activated neutrophils. The conclusion was that lipopolysaccharides induce an up-regulation of inflammatory mediators and signaling molecules, as well as the remodeling of the cytoskeleton, which may explain the release of secretory granules and the migration of neutrophils towards the site of infection [138]. The central pathway in the regulation of neutrophil function is the p38 mitogen-activated protein kinase signal transduction as shown by Singh et al [139].…”

Section: Leukocytesmentioning

confidence: 99%

Recent advances in blood‐related proteomics

et al. 2005

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Service régional vaudois de transfusion sanguine, Lausanne, SwitzerlandBlood is divided in two compartments, namely, plasma and cells. The latter contain red blood cells, leukocytes, and platelets. From a descriptive medical discipline, hematology has evolved towards a pioneering discipline where molecular biology has permitted the development of prognostic and diagnostic indicators for disease. The recent advance in MS and protein separation now allows similar progress in the analysis of proteins. Proteomics offers great promise for the study of proteins in plasma/serum, indeed a number of proteomics databases for plasma/ serum have been established. This is a very complex body fluid containing lipids, carbohydrates, amino acids, vitamins, nucleic acids, hormones, and proteins. About 1500 different proteins have recently been identified, and a number of potential new markers of diseases have been characterized. Here, examples of the enormous promise of plasma/serum proteomic analysis for diagnostic/prognostic markers and information on disease mechanism are given. Within the blood are also a large number of different blood cell types that potentially hold similar information. Proteomics of red blood cells, until now, has not improved our knowledge of these cells, in contrast to the major progresses achieved while studying platelets and leukocytes. In the future, proteomics will change several aspects of hematology.

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A Genomic and Proteomic Analysis of Activation of the Human Neutrophil by Lipopolysaccharide and Its Mediation by p38 Mitogen-activated Protein Kinase

Cited by 160 publications

References 66 publications

Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2–ASK1 signals

Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2–ASK1 signals

Enhanced neutrophil extravasation and rapid progression of proteoglycan‐induced arthritis in TSG‐6–knockout mice

Recent advances in blood‐related proteomics

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