ERK MAP Kinase Links Cytokine Signals to Activation of Latent HIV-1 Infection by Stimulating a Cooperative Interaction of AP-1 and NF-κB

Yang, Xiaoyu; Chen, Youzhi; Gabuzda, Dana

doi:10.1074/jbc.274.39.27981

Cited by 184 publications

(158 citation statements)

References 81 publications

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“…The present study demonstrates an intimate cross-talk between the NF-B and Erk1/2 pathways in iNOS expression. This is supported by several reports that NF-B transcriptional activity is controlled by Erk1/2 MAP kinase (33)(34)(35)(36). In addition, the signaling pathways with p38 MAP kinase and SAPK/JNK MAP kinase are reported to be involved in LPS-induced iNOS expression (13,37).…”

Section: Discussionsupporting

confidence: 73%

The Inhibitory Action of Sodium Arsenite on Lipopolysaccharide-Induced Nitric Oxide Production in RAW 267.4 Macrophage Cells: A Role of Raf-1 in Lipopolysaccharide Signaling

Chakravortty

Kato

Sugiyama

et al. 2001

The Journal of Immunology

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The effect of sodium arsenite (SA) on LPS-induced NO production in RAW 267.4 murine macrophage cells was studied. SA pretreatment of LPS-stimulated RAW cells resulted in a striking reduction in NO production. No significant difference in LPS binding was observed between RAW cells pretreated with SA and control untreated RAW cells, suggesting that SA might impair the intracellular signal pathway for NO production. SA inhibited LPS-induced NF-κB activation by preventing loss of IκB-α and -β. Furthermore, SA blocked phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), but not phosphorylation of p38 and c-Jun N-terminal kinase. SA treatment resulted in the disappearance of Raf-1, suggesting that it might cause the inhibition of the Erk1/2 mitogen-activated protein (MAP) kinase pathway. The SA-mediated loss of Raf-1 also abolished LPS-induced NF-κB activation as well as the Erk1/2 pathway. The dominant negative mutant of MAP kinase kinase 1 inhibited both NO production and NF-κB activation in LPS-stimulated RAW cells. Taken together, these results indicate that the inhibitory action of SA on NO production in LPS-stimulated macrophages might be due to abrogation of inducible NO synthase induction, and it might be closely related to inactivation of the NF-κB and Erk1/2 MAP kinase pathways through loss of Raf-1.

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Section: Discussionsupporting

confidence: 73%

The Inhibitory Action of Sodium Arsenite on Lipopolysaccharide-Induced Nitric Oxide Production in RAW 267.4 Macrophage Cells: A Role of Raf-1 in Lipopolysaccharide Signaling

Chakravortty

Kato

Sugiyama

et al. 2001

The Journal of Immunology

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“…Therefore, although putative sites for AP-1 have been described in the human TGF␤RII promoter (46), AP-1 proteins could act through other sites. For example, AP-1 protein has previously been shown to cooperate individually with RelA proteins at the NF-B site of the promoter of specific cellular genes (47,48). However, it is not clear whether p65 and AP-1 were recruited to the native TGF␤RII promoter.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐1β impairment of transforming growth factor β1 signaling by DOWN‐REGULATION of transforming growth factor β receptor type II and up‐regulation of Smad7 in human articular chondrocytes

Baugé

Legendre

Leclercq

et al. 2007

Arthritis & Rheumatism

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Objective. Extracellular matrix deposition is tightly controlled by a network of regulatory cytokines. Among them, interleukin-1␤ (IL-1␤) and transforming growth factor ␤1 (TGF␤1) have been shown to play antagonistic roles in tissue homeostasis. The purpose of this study was to determine the influence of IL-1␤ on TGF␤ receptor type II (TGF␤RII) regulation and TGF␤1 responsiveness in human articular chondrocytes.Methods. TGF␤1-induced gene expression was analyzed through plasminogen activator inhibitor 1 and p3TP-Lux induction. Receptor-activated Smad (RSmad) phosphorylation, TGF␤ receptors, and Smad expression were determined by Western blotting and real-time reverse transcription-polymerase chain reaction techniques. Signaling pathways were investigated using specific inhibitors, messenger RNA (mRNA) silencing, and expression vectors.Results. IL-1␤ down-regulated TGF␤RII expression at both the protein and mRNA levels and led to inhibition of the TGF␤1-induced gene expression and Smad2/3 phosphorylation. Moreover, IL-1␤ strongly stimulated the expression of inhibitory Smad7.TGF␤RII overexpression abolished the loss of TGF␤1 responsiveness induced by IL-1␤. The decrease in TGF␤RII required de novo protein synthesis and involved both the NF-B and JNK pathways.Conclusion. We demonstrate that IL-1␤ impairs TGF␤1 signaling through down-regulation of TGF␤RII, which is mediated by the p65/NF-B and activator protein 1/JNK pathways, and secondarily through the up-regulation of Smad7. These findings show that there is cross-talk in the signaling of 2 regulatory cytokines involved in inflammation.

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“…In this regard, our original description of the differential features of IL-6-vs TNF-␣-induced HIV expression pointed out to a major role of posttranscriptional events in IL-6-mediated up-regulation of viral production from U1 cells (12). Alternatively, PTX-B could downregulate AP-1 mediated activation of the intragenic gag enhancer (48,60), previously suggested to be induced by stimuli, such as IL-6, in combination with TNF-␣ or glucocorticoids (38,49). In this regard, our findings on the levels of luciferase expression driven by LTRs after IL-6 stimulation add to previous reports on biological differences among the different HIV clades, which are determined in part by differences in the composition of the LTR promoter (52,(77)(78)(79)(80).…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that STAT3 activation induced by IL-6 leads to heterodimerization with constitutively activated STAT1 (middle complex), as previously described (45). A second family of transcription factors known to be induced upon IL-6 stimulation in different cell types, including monocytic cells, is the dimeric transcription factor AP-1 (46, 47) that has been previously associated with increased transcription and expression of HIV in different cell systems (48), including U1 cells (38,49). Based on our preliminary experiments (C. Rizzi, unpublished observation) as well as published evidence (38,49), AP-1 binding to DNA becomes clearly evident 20 h after IL-6 stimulation.…”

Section: Ptx-b Inhibits Il-6-induced Activation Of Ap-1 But Not Of Smentioning

confidence: 99%

Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

Rizzi

Crippa²,

Jeeninga

et al. 2006

The Journal of Immunology

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Pertussis toxin B-oligomer (PTX-B) inhibits HIV replication in T lymphocytes and monocyte-derived macrophages by interfering with multiple steps of the HIV life cycle. PTX-B prevents CCR5-dependent (R5) virus entry in a noncompetitive manner, and it also exerts suppressive effects on both R5- and CXCR4-dependent HIV expression at a less-characterized postentry level. We demonstrate in this study that PTX-B profoundly inhibits HIV expression in chronically infected promonocytic U1 cells stimulated with several cytokines and, particularly, the IL-6-mediated effect, a cytokine that triggers viral production in these cells independently of NF-κB activation. From U1 cells we have subcloned a cell line, named U1-CR1, with increased responsiveness to IL-6. In these cells, PTX-B neither down-regulated the IL-6R nor prevented IL-6 induced signaling in terms of STAT3 phosphorylation and DNA binding. In contrast, PTX-B inhibited AP-1 binding to target DNA and modified its composition with a proportional increases in FosB, Fra2, and ATF2. PTX-B inhibited IL-6-induced HIV-1 long-terminal repeat-driven transcription from A, C, E, and F viral subtypes, which contain functional AP-1 binding sites, but failed to inhibit transcription from subtypes B and D LTR devoid of these sites. In addition, PTX-B inhibited the secretion of IL-6-induced, AP-1-dependent genes, including urokinase-type plasminogen activator, CXCL8/IL-8, and CCL2/monocyte chemotactic protein-1. Thus, PTX-B suppression of IL-6 induced expression of HIV and cellular genes in chronically infected promonocytic cells is strongly correlated to inhibition of AP-1.

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ERK MAP Kinase Links Cytokine Signals to Activation of Latent HIV-1 Infection by Stimulating a Cooperative Interaction of AP-1 and NF-κB

Cited by 184 publications

References 81 publications

The Inhibitory Action of Sodium Arsenite on Lipopolysaccharide-Induced Nitric Oxide Production in RAW 267.4 Macrophage Cells: A Role of Raf-1 in Lipopolysaccharide Signaling

The Inhibitory Action of Sodium Arsenite on Lipopolysaccharide-Induced Nitric Oxide Production in RAW 267.4 Macrophage Cells: A Role of Raf-1 in Lipopolysaccharide Signaling

Interleukin‐1β impairment of transforming growth factor β1 signaling by DOWN‐REGULATION of transforming growth factor β receptor type II and up‐regulation of Smad7 in human articular chondrocytes

Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

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