Requirement for p38 and p44/p42 Mitogen-Activated Protein Kinases in RAGE-Mediated Nuclear Factor-κB Transcriptional Activation and Cytokine Secretion

Yeh, Chen‐Hsiung; Sturgis, Lydia; Haidacher, Joe; Zhang, Xue Nong; Sherwood, Sidney J.; Bjercke, Robert J.; Juhász, Ondrej; Crow, Michael T.; Tilton, Ronald G.; Denner, Larry

doi:10.2337/diabetes.50.6.1495

Cited by 314 publications

(199 citation statements)

References 58 publications

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“…Soluble RAGE [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] (sRAGE) and the reverse peptide were synthesized by manual solid-phase synthesis using 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate-mediated couplings with Boc in situ neutralization chemistry (27) and purified by preparative reverse-phase HPLC using a C 18 column. Fractions containing the pure proteins were rerun on analytical HPLC, and masses were confirmed by electrospray ionization mass spectrometry (21,765.5 Ϯ 1.0, calculated: 2,177.2).…”

Section: Reagentsmentioning

confidence: 99%

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Serum Amyloid A Induces Monocyte Tissue Factor

Cai

Song

Endoh

et al. 2007

The Journal of Immunology

107

121

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C-reactive protein (CRP) and serum amyloid A (SAA) increase in the blood of patients with inflammatory conditions and CRP-induced monocyte tissue factor (TF) may contribute to inflammation-associated thrombosis. This study demonstrates that SAA is a potent and rapid inducer of human monocyte TF. SAA induced TF mRNA in PBMC within 30 min and optimal procoagulant activity within 4 h, whereas CRP (25 μg/ml)-induced activity was minimal at this time. Unlike CRP, SAA did not synergize with LPS. Procoagulant activity was inhibited by anti-TF and was dependent on factors VII and X, and TF Ag levels were elevated on CD14+ monocytes. Responses were optimal with lymphocytes, although these were not obligatory. Inhibitor studies indicate activation of NF-κB through the ERK1/2 and p38 MAPK pathways; the cyclo-oxygenase pathway was not involved. SAA-induced TF was partially inhibited by high-density lipoprotein, but not by low-density lipoprotein or by apolipoprotein A-I. SAA is a ligand for the receptor for advanced glycation end products (RAGE), and TF generation was suppressed by ∼50% by a RAGE competitor, soluble RAGE, and by ∼85% by anti-RAGE IgG. However, another RAGE ligand, high mobility group box-1 protein, capable of inducing monocyte chemotactic protein-1 mRNA in 2 h, did not induce TF within 24 h. Cross-linking studies confirmed SAA binding to soluble RAGE. Elevated SAA is a marker of disease activity in patients with rheumatoid arthritis, and PBMC from patients with rheumatoid arthritis were more sensitive to SAA than normals, suggesting a new link between inflammation and thrombosis.

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Section: Reagentsmentioning

confidence: 99%

“…To determine whether induction may occur via RAGE, SAA or LPS was preincubated with sRAGE [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] peptide antagonist containing the RAGE ligand-binding domain, and PBMC was stimulated 2 h later. Fig.…”

Section: Mechanisms Of Tf Induction By Saamentioning

confidence: 99%

Serum Amyloid A Induces Monocyte Tissue Factor

Cai

Song

Endoh

et al. 2007

The Journal of Immunology

107

121

View full text Add to dashboard Cite

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“…Indeed, increased levels of TNF-α and TGF-β1 have been detected in the serum or glomeruli of diabetic rodents [16,17] and serum levels of these cytokines are increased in diabetic patients [18]. Furthermore, advanced glycation, glycoxidation and lipoxidation end-products can stimulate IL-1 and TNF-α production by macrophages [19,20]. IL-1 and TNF-α are potent inducers of p38 MAPK in renal parenchymal cells [6,21] and TGF-β1 stimulates p38 MAPK phosphorylation in mesangial cells and fibroblasts [7,8].…”

Section: Introductionmentioning

confidence: 99%

Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy

et al. 2004

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Aims/hypothesis. Inflammation and fibrosis are pathological mechanisms that are partially regulated by cell signalling through the p38 mitogen-activated protein kinase (MAPK) pathway. Elements of the diabetic milieu such as high glucose and advanced glycation endproducts induce activation of this pathway in renal cells. Therefore, we examined whether p38 MAPK signalling is associated with the development of human and experimental diabetic nephropathy. Methods. Immunostaining identified phosphorylated (active) p38 MAPK in human biopsies with no abnormality (n=6) and with Type 2 diabetic nephropathy (n=12). Changes in kidney levels of phosphorylated p38 were assessed by immunostaining and western blotting in mice with streptozotocin-induced Type 1 diabetes that had been killed after 0.5, 2, 3, 4 and 8 months, and in Type 2 diabetic db/db mice at 2, 4, 6 and 8 months of age. Results. Phosphorylated p38 was detected in some intrinsic cells in normal human kidney, including podocytes, cortical tubules and occasional interstitial cells. Greater numbers of these phosphorylated p38+ cells were observed in diabetic patients, and phosphorylated p38 was identified in accumulating interstitial macrophages and myofibroblasts. A similar pattern of p38 activation was observed in both mouse models of diabetes. In mice, kidney levels of phosphorylated p38 increased (2-6 fold) following the onset of Type 1 and Type 2 diabetes. In both mouse models, interstitial phosphorylated p38+ cells were associated with hyperglycaemia, increased HbA 1 c levels and albuminuria. Further assessment of streptozotocin-induced diabetic nephropathy showed that interstitial phosphorylated p38+ cells correlated with interstitial fibrosis (myofibroblasts, collagen). Conclusions/interpretation. Increased p38 MAPK signalling is a feature of human and experimental diabetic nephropathy. Time course studies in mouse models suggest that phosphorylation of p38 plays a pathological role, particularly in the development of interstitial fibrosis.

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“…The detrimental effects of AGEs in diabetic and non-diabetic nephropathy have been intensively investigated recently [6]. In vivo, CML is the most widely distributed AGE under oxidative conditions and can exert cellular effects by binding to the AGE receptor RAGE [7][8][9]. Its age-dependent tissue accumulation is accelerated in patients with diabetes mellitus, and serum CML levels correlate with loss of renal function in diabetic patients [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition

Wihler¹,

Schäfer²,

Schmid³

et al. 2005

Diabetologia

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Aims/hypothesis: Renal accumulation of AGEs may contribute to the progression of diabetic nephropathy. We evaluated the effect of ramipril (a pure ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidase) on renal accumulation of the advanced glycation end-product (AGE) 3-deoxyglucosone-imidazolone, carboxymethyllysine (CML) and pentosidine, and on clearance of CML in type 2 diabetes. Methods: Male Zucker diabetic fatty rats (ZDF, Gmi-fa/fa) rats were treated from age 10 to 37 weeks with ramipril (1 mg·kg −1 ·day −1 ), AVE7688 (45 mg·kg −1 ·day −1 ) or without drug. Ramipril and AVE7688 reduced albuminuria by 30 and 90%, respectively. Results: ZDF rats showed increased renal accumulation of the AGE subtypes 3-deoxyglucosone-imidazolone, pentosidine and CML by about 40, 55 and 55%, respectively compared with heterozygous, non-diabetic control animals at the age of 37 weeks. AVE7688 but not ramipril attenuated the renal accumulation of 3-deoxyglucosone-imidazolone, pentosidine and CML and improved CML clearance in ZDF rats. During glycation reactions in vitro, AVE7688 also demonstrated potent chelating activity and inhibited metal-catalysed formation of pentosidine and CML. Conclusions/interpretation: Improved AGE clearance and direct inhibition of AGE formation by chelation may contribute to reduced accumulation of renal AGEs and to the nephroprotective effects of vasopeptidase inhibition in type 2 diabetes.

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Requirement for p38 and p44/p42 Mitogen-Activated Protein Kinases in RAGE-Mediated Nuclear Factor-κB Transcriptional Activation and Cytokine Secretion

Cited by 314 publications

References 58 publications

Serum Amyloid A Induces Monocyte Tissue Factor

Serum Amyloid A Induces Monocyte Tissue Factor

Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy

Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition

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