Stimulus-specific regulation of chemokine expression involves differential activation of the redox-responsive transcription factors AP-1 and NF-κB

Roebuck, Kenneth A.; Carpenter, Laura Rocco; Lakshminarayanan, Venkatesh; Page, Scott M.; Moy, James N.; Thomas, Larry L.

doi:10.1002/jlb.65.3.291

Cited by 216 publications

(160 citation statements)

References 67 publications

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“…Neither C/EBP␤ nor AP-1/c-Jun contributed to the expression of the IL-8 gene, in either RA FLS or HDF, despite the activation of both C/EBP␤ and AP-1 in RA FLS. It is possible that C/EBP␤ or c-Jun may contribute to the expression of IL-8 in other cell types or when the cells are stimulated differently (24,48). Nonetheless, our observations do not exclude a potential interaction of NF-B with AP-1 or C/EBP␤ (19 -21, 24, 28, 48).…”

Section: Discussionmentioning

confidence: 58%

Regulation of IL-6 and IL-8 Expression in Rheumatoid Arthritis Synovial Fibroblasts: the Dominant Role for NF-κB But Not C/EBPβ or c-Jun

Georganas

Liu

Perlman

et al. 2000

The Journal of Immunology

200

134

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Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) produce IL-6 and IL-8, which contribute to inflammation and joint damage. The promoters of both cytokines possess binding sites for NF-κB, C/EBPβ, and c-Jun, but the contribution of each to the regulation of IL-6 and IL-8 in RA FLS is unknown. We employed adenoviral-mediated gene delivery of a nondegradable IκBα, or dominant-negative versions of C/EBPβ or c-Jun, to determine the contribution of each transcription factor to IL-6 and IL-8 expression. Inhibition of NF-κB activation significantly reduced the spontaneous and IL-1β-induced secretion of IL-6 and IL-8 by RA FLS and the IL-1β-induced production of IL-6 and IL-8 by human dermal fibroblasts. Inhibition of C/EBPβ modestly reduced constitutive and IL-1β-induced IL-6 by RA FLS, but not by human dermal fibroblasts, and had no effect on IL-8. Inhibition of c-Jun/AP-1 had no effect on the production of either IL-6 or IL-8. Employing gel shift assays, NF-κB, C/EBPβ, and c-Jun were constitutively activated in RA FLS, but only NF-κB and c-Jun activity increased after IL-1β. The reduction of cytokines by IκBα was mediated through inhibition of NF-κB activation, which resulted in decreased IL-6 and IL-8 mRNA. NF-κB was essential for IL-6 expression, because fibroblasts in which both NF-κB p50/p65 genes were deleted failed to express IL-6 in response to IL-1. These findings document the importance of NF-κB for the regulation of the constitutive and IL-1β-stimulated expression of IL-6 and IL-8 by RA FLS and support the role of inhibition of NF-κB as a therapeutic goal in RA.

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Section: Discussionmentioning

confidence: 58%

Regulation of IL-6 and IL-8 Expression in Rheumatoid Arthritis Synovial Fibroblasts: the Dominant Role for NF-κB But Not C/EBPβ or c-Jun

Georganas

Liu

Perlman

et al. 2000

The Journal of Immunology

200

134

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“…AP-1-dependent transcription may lead to the up-regulation of several cytokines (54), including the chemokines CXCL8/IL-8 and CCL2/MCP-1. The secretion of both chemokines is up-regulated after in vitro HIV infection of primary PBMCs and MDM (56,81) or after IL-6 stimulation of MDM and promonocytic U1 and U937 cells (15).…”

Section: Discussionmentioning

confidence: 99%

“…7A). To correlate this strong inhibitory effect to that of other cellular genes, we investigated PTX-B's capacity to interfere with chemokines such as CXCL8/IL-8 and CCL2/MCP-1, which are transcriptionally regulated by AP-1 (53,54) and can up-regulate HIV replication both in vitro (16,(55)(56)(57) and in vivo (58). Neither chemokine was detectable in the culture supernatants of either unstimulated or PTX-B-stimulated U1 (data not shown) and U1-CR1 (Fig.…”

Section: Ptx-b Prevents Hiv Production and Cxcl8/il-8 And Ccl2/ Mcp-1mentioning

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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“…8 Extensive evidence supports a role for reactive oxygen in chemokine induction chemokines in various cell types; however, this observation is confounded by significant variability of response to ROI with regard to cell type and chemokine species. 17,19 Nevertheless, the possibility that reactive oxygen might be responsible for the induction of MCP-1 localized in the venules was considered because: 1) H 2 O 2 is capable of inducing MCP-1 mRNA in endothelial cells, 1,36 2) ROI formation is induced during early reperfusion of the myocardium, 12,14,37 and 3) ROIs from the reperfused myocardium egress to the capillary vascular bed.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17] The observation that ROIs may act as transcriptional activators is complicated by the fact that transcriptional regulation of ROI-mediated chemokine genes varies greatly with cell type. [17][18][19] For example, the ROI H 2 O 2 differentially regulates chemokine expression in a cell-type, gene-type-specific manner in A549 epithelial cells through the transcription factor AP-1, however, it does not induce IL-8 in endothelial cells. 17,18 Similarly, generation of ROIs with xanthine/ xanthine oxidase induced IL-8 and MCP-1 production from monocytes, but not U937 cells, and this induction is associated with increased NF-B DNA binding.…”

mentioning

confidence: 99%

Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

Lakshminarayanan

Lewallen

Frangogiannis

et al. 2001

The American Journal of Pathology

Self Cite

102

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Monocyte chemotactic protein (MCP)-1 is a member of the CC chemokine family and serves as a chemotactic factor for the recruitment of monocytes and subpopulations of T cells during inflammation. 1 It is induced by the proinflammatory cytokines interleukin (IL)-1␤ and tumor necrosis factor (TNF)-␣, as well as phorbol esters, which regulate its induction at the transcriptional level through the cooperative interaction of the transcription factors AP-1 and nuclear factor (NF)-B. 2-4 Specifically, in endothelial cells, IL-1␤, TNF-␣, and phorbol esters mediate human MCP-1 gene expression through the cooperative interaction of the NF-B binding site at Ϫ90 bp (relative to the start site) and the AP-1 binding site at Ϫ68 bp. 2,3 Early reperfusion of the ischemic myocardium is a key clinical intervention after myocardial infarction and is attended by a robust inflammatory reaction involving both neutrophils and mononuclear cells. 5,6 It has been shown that late reperfusion, when myocardial salvage is no longer possible, improves myocardial repair and obviates infarct expansion.

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Stimulus-specific regulation of chemokine expression involves differential activation of the redox-responsive transcription factors AP-1 and NF-κB

Cited by 216 publications

References 67 publications

Regulation of IL-6 and IL-8 Expression in Rheumatoid Arthritis Synovial Fibroblasts: the Dominant Role for NF-κB But Not C/EBPβ or c-Jun

Regulation of IL-6 and IL-8 Expression in Rheumatoid Arthritis Synovial Fibroblasts: the Dominant Role for NF-κB But Not C/EBPβ or c-Jun

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

Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

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