Hypoxia/reoxygenation induction of monocyte chemoattractant protein-1 in melanoma cells: involvement of nuclear factor-κB, stimulatory protein-1 transcription factors and mitogen-activated protein kinase pathways

Kunz, Manfred; Bloss, G; Gillitzer, R.; Gross, Gerd; Goebeler, Matthias; Rapp, Ulf R.; Ludwig, Stephan

doi:10.1042/bj20011749

Cited by 23 publications

(24 citation statements)

References 41 publications

(57 reference statements)

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“…Increased MCP-1 mRNA and protein expression was reported in human dermal fibroblasts exposed to hypoxia (44), and human melanoma cell lines were shown to up-regulate MCP-1 mRNA and protein under anoxia/reoxygenation (45). Moreover, stimulatory effects of hypoxia on MCP-1 have been observed in ischemic rat neurons and myocardial cells (46,47).…”

Section: Discussionmentioning

confidence: 87%

“…Interestingly, we found by computer search of the published MCP-1 promoter sequence (GenBank accession number U12470) a region of homology with the HRE (hereafter referred to as MCP-HRE) present in the promoter of many hypoxia-inducible genes (20,22,23), comprizing both an HIF-1 binding site (sequence GGCGTGGT; Ϫ1639/Ϫ1632) and a downstream HIF-1 ancillary sequence (sequence CACGC; Ϫ1626/ Ϫ1622) required for the interaction with additional transcription factors (54). At present, the role of MCP-HRE in the regulation of MCP-1 expression is not clear, because MCP-1 transcriptional induction by hypoxia in human melanoma cell lines and dermal fibroblasts was shown to be dependent on the activation of NF-B and Sp-1 binding motifs (44,45). Experiments are underway in our laboratory to determine whether MCP-1-HRE is active in the control of MCP-1 transcription by hypoxia in M.…”

Section: Discussionmentioning

confidence: 93%

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Hypoxia Selectively Inhibits Monocyte Chemoattractant Protein-1 Production by Macrophages

Bosco

Puppo

Pastorino

et al. 2004

The Journal of Immunology

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Hypoxia, a local decrease in oxygen tension occurring in inflammatory and tumor lesions, modulates gene expression in macrophages. Because macrophages are important chemokine producers, we investigated the regulatory effects of hypoxia on macrophage-derived chemokines. We demonstrated that hypoxia inhibits the production of the macrophage and T lymphocyte chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1). Exposure of mouse macrophages to low oxygen tension resulted in the down-regulation of constitutive MCP-1 mRNA expression and protein secretion. Hypoxia inhibitory effects were selective for MCP-1 because the chemokines macrophage inflammatory protein-1β (MIP-1β), RANTES, IFN-γ-inducible protein-10, and MIP-2 were not affected, and MIP-1α was induced. Hypoxia also inhibited, in a time-dependent fashion, MCP-1 up-regulation by IFN-γ and LPS. Moreover, the inhibitory action of hypoxia was exerted on human monocytic cells. MCP-1 down-regulation was associated with inhibition of gene transcription and mRNA destabilization, suggesting a dual molecular mechanism of control. Finally, we found that the triptophan catabolite picolinic acid and the iron chelator desferrioxamine, which mimic hypoxia in the induction of gene expression, differentially regulated the expression of MCP-1. This study characterizes a novel property of hypoxia as a selective inhibitor of MCP-1 production induced by different stimuli in macrophages and demonstrates that down-regulation of gene expression by hypoxia can be controlled at both transcriptional and posttranscriptional levels. Inhibition of MCP-1 may represent a negative regulatory mechanism to control macrophage-mediated leukocyte recruitment in pathological tissues.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 93%

Hypoxia Selectively Inhibits Monocyte Chemoattractant Protein-1 Production by Macrophages

Bosco

Puppo

Pastorino

et al. 2004

The Journal of Immunology

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“…42 The formation of MCP-1 is reduced by hypoxia in ovarian cancer cells, 43 macrophages 44,45 and human synovial fibroblasts. 46 However, hypoxia upregulated MCP-1 formation in cultured neonatal mouse cardiac myocytes and MCP-1 decreased hypoxia-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity. OBJECTIVE: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor a (TNFa) and IL-1b based on the ability of a combination of a soluble TNFa receptor (etanercept) and a blocking antibody against IL-1b to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kB (NF-kB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kB pathways was greater than that seen with only the NF-kB inhibitor. DISCUSSION: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFa and Il-1b and involves the p38 MAPK and NF-kB pathways.

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“…27,40 This finding is consistent with the selectivity of TGF␤-mediated suppression; IP-10 and MCP-1 mRNA expression are unaffected by TGF␤, though transcription of both depends upon activation of NFB. 22,41 Indeed, the kinetic patterns of expression of KC and MIP-2 mRNAs versus IP-10 and MCP-1 mRNAs are quite distinct, suggesting the mechanistic difference (Figure 1). Prior studies have shown that TGF␤-mediated suppression of interferon ␥-, IL-1␣-, or TNF␣-stimulated transcription does not involve interference with signaling responses or transcription factor activation to any of these stimulatory agents.…”

Section: Discussionmentioning

confidence: 99%

TGFβ inhibits LPS-induced chemokine mRNA stabilization

Dai

Datta

Novotny

et al. 2003

Blood

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The mechanisms involved in anti-inflammatory action of transforming growth factor ␤ (TGF␤) have been examined by evaluating its effect on chemokine gene expression in mouse macrophages. Lipopolysaccharide (LPS)-stimulated expression of the CXC chemokines KC and MIP-2 was selectively reduced by TGF␤ in a time-and protein synthesis-dependent process. While TGF␤ had a modest effect on transcription of the KC and MIP-2 mRNAs as measured by nuclear run-on, it had no effect on LPS-stimulated luciferase expression driven by the KC promoter nor on the activation of nuclear factor B (NFB) DNA-binding activity and transactivation function. Interestingly, KC mRNA levels were markedly reduced by TGF␤ treatment in cells transfected with KC genomic or cDNA constructs driven from either the KC or cytomegalovirus (CMV) promoters, demonstrating the importance of sequences within the mature mRNA and suggesting that suppression may involve a posttranscriptional mechanism. In support of this possibility, LPS stimulation prolonged the half-life of KC mRNA and this stabilization response was blocked in cells treated with TGF␤. Examination of KC mRNA expressed under control of a tetracycline-responsive promoter demonstrated that TGF␤ prevented stabilization of KC mRNA, in response to LPS but did not alter KC mRNA half-life directly. KC mRNA stabilization by LPS was dependent on activation of p38 mitogen-activated protein kinase (MAPK) activity, and TGF␤ treatment inhibited p38 MAPK activation. These findings support the hypothesis that TGF␤-mediated suppression of chemokine gene expression involves antagonism of LPS-stimulated KC mRNA stabilization via inhibition of p38 MAPK.

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Hypoxia/reoxygenation induction of monocyte chemoattractant protein-1 in melanoma cells: involvement of nuclear factor-κB, stimulatory protein-1 transcription factors and mitogen-activated protein kinase pathways

Cited by 23 publications

References 41 publications

Hypoxia Selectively Inhibits Monocyte Chemoattractant Protein-1 Production by Macrophages

Hypoxia Selectively Inhibits Monocyte Chemoattractant Protein-1 Production by Macrophages

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

TGFβ inhibits LPS-induced chemokine mRNA stabilization

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