Differential induction of monocyte chemotactic protein-3 in mononuclear leukocytes and fibroblasts by interferon-α / β and interferon-γ reveals MCP-3 heterogeneity

Menten, Patricia; Proost, Paul; Struyf, Sofie; Coillie, Els Van; Put, Willy; Lenaerts, Jean‐Pierre; Conings, René; Jaspar, Jean-Marie; Groote, Donat De; Billiau, Alfons; Opdenakker, Ghislain; Damme, Jo Van

doi:10.1002/(sici)1521-4141(199902)29:02<678::aid-immu678>3.0.co;2-j

Cited by 66 publications

(49 citation statements)

References 19 publications

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“…In contrast to the synergistic effect of IFN-␥ on IL-1␤-induced MCP-2 and MCP-3 production (Menten et al, 1999;Struyf et al, 1998), IFN-␥ diminished the GCP-2 production in fibroblasts stimulated with IL-1␤, TNF-␣, dsRNA, and LPS. Similar to the GCP-2 induction, the IL-8 production induced by TNF-␣ was decreased by IFN-␥.…”

Section: Regulation Of Gcp-2 In Connective Tissuementioning

confidence: 95%

“…Because IL-1␤ has been reported to synergize with other cytokines such as IFN-␥ (Menten et al, 1999;Struyf et al, 1998), which failed to induce GCP-2, the effect of simultaneous addition of different stimuli on GCP-2 production by fibroblasts was evaluated. First, these experiments confirm the induction of GCP-2 and IL-8 protein in fibroblasts (Figs.…”

Section: Down-regulation Of Gcp-2 Production In Fibroblasts By Ifn-␥mentioning

confidence: 99%

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The CXC Chemokine GCP-2/CXCL6 Is Predominantly Induced in Mesenchymal Cells by Interleukin-1β and Is Down-Regulated by Interferon-γ: Comparison with Interleukin-8/CXCL8

Wuyts

Struyf

Gijsbers

et al. 2003

Laboratory Investigation

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SUMMARY:Human granulocyte chemotactic protein-2 (GCP-2)/CXCL6 is a CXC chemokine that functionally uses both of the IL-8/CXCL8 receptors to chemoattract neutrophils but that is structurally most related to epithelial cell-derived neutrophil attractant-78 (ENA-78)/CXCL5. This study provides the first evidence that GCP-2 protein is, compared with IL-8, weakly produced by some sarcoma, but less by carcinoma cells, and is tightly regulated in normal mesenchymal cells. IL-1␤ was the predominant GCP-2 inducer in fibroblasts, chondrocytes, and endothelial cells, whereas IL-8 was equally well up-regulated in these cells by TNF-␣, measles virus, or double-stranded RNA (dsRNA). In contrast, lipopolysaccharide (LPS) was a relatively better stimulus for GCP-2 versus IL-8 in fibroblasts. IFN-␥ down-regulated the GCP-2 production in fibroblasts induced by IL-1␤, TNF-␣, LPS, or dsRNA. The kinetics of GCP-2 induction by IL-1␤, LPS, or dsRNA in fibroblasts differed from those of IL-8. Freshly isolated peripheral blood mononuclear leukocytes, which are a good source of IL-8 and ENA-78, failed to produce GCP-2. However, lung macrophages and blood monocyte-derived macrophages produced GCP-2 in response to LPS. Quantitatively, secretion of GCP-2 always remained inferior to that of IL-8, despite the fact that the ELISA recognized all posttranslationally modified GCP-2 isoforms. The expression of GCP-2 was confirmed in vivo by immunohistochemistry. The patterns of producer cell types, inducers and kinetics and the quantities of GCP-2 produced, suggest a unique role for GCP-2 in physiologic and pathologic processes. (Lab Invest 2003, 83:23-34).

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Section: Regulation Of Gcp-2 In Connective Tissuementioning

confidence: 95%

Section: Down-regulation Of Gcp-2 Production In Fibroblasts By Ifn-␥mentioning

confidence: 99%

The CXC Chemokine GCP-2/CXCL6 Is Predominantly Induced in Mesenchymal Cells by Interleukin-1β and Is Down-Regulated by Interferon-γ: Comparison with Interleukin-8/CXCL8

Wuyts

Struyf

Gijsbers

et al. 2003

Laboratory Investigation

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“…), frozen at 280°C until analysis and their chemokine content determined by a specific ELISA. 9 For the daily chemokine production, the medium was removed, frozen and replaced by fresh medium.…”

Section: Virus Titrationsmentioning

confidence: 99%

“…However, our attempts to biochemically isolate and identify from these cell supernatants (a) major active form(s) of parvovirus-delivered MCP-3 were not successful. Indeed, similar to MCP-3 forms isolated from normal cells, 9 several different forms of posttranslationally modified MCP-3 (e.g. by glycosylation) were found to be expressed by parvovirus-infected B78/H1 or K1735 melanoma cells, preventing us to isolate purified single forms of MCP-3 in sufficient amounts for biochemical analysis.…”

Section: Tumor Growth Of Mcp-3-transfected B78/h1 Melanoma Cellsmentioning

confidence: 99%

“…8 Accordingly, MCP-3 was shown to be a potent chemoattractant for a variety of leukocytes including monocytes, eosinophils, basophils, DC, NK cells and activated T lymphocytes. 8,9 The central roles that DC and distinct T lymphocyte populations play in acquiring tumor immunity, make MCP-3 an appealing antitumor agent. This assumption could be confirmed as subcutaneously implanted mouse mastocytoma cells, engineered to release human MCP-3, were rejected in immunocompetent mice or grew at a strongly reduced rate.…”

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confidence: 99%

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MCP‐3 (CCL7) delivered by parvovirus MVMp reduces tumorigenicity of mouse melanoma cells through activation of T lymphocytes and NK cells

Wetzel

Struyf

Damme

et al. 2006

Intl Journal of Cancer

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Monocyte chemotactic protein 3 (MCP-3/CCL7), a CC chemokine able to attract and activate a large panel of leukocytes including natural killer cells and T lymphocytes, could be beneficial in antitumor therapy. Vectors were constructed based on the autonomous parvovirus minute virus of mice (MVMp), carrying the human (MCP-3) cDNA. These vectors were subsequently evaluated in the poorly immunogenic mouse melanoma model B78/ H1. The infection of the tumor cells with MCP3-transducing vector at low virus input multiplicities, but not with wild-type virus, strongly inhibited tumor growth after implantation in euthymic mice. In a therapeutic B78/H1 model, repeated intratumoral injections of MCP3-tranducing virus prevented further tumor expansion as long as the treatment was pursued. The antitumor effects of the MCP-3-transducing vector were not restricted to this tumor model since they could also be observed in the K1735 melanoma.

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IRAK‐4 kinase activity‐dependent and ‐independent regulation of lipopolysaccharide‐inducible genes

et al. 2008

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IRAK-4 kinase inactive (IRAK-4 KD) knock-in mice display defects in TLR-and IL-1 receptor signaling and are resistant to LPS-induced shock. In the present study we examined the LPS-induced response in IRAK-4 KD mice in more detail. We show that IRAK-4 kinase activity is required for certain aspects of TLR-mediated signaling but not for others. We found that IRAK-4 KD cells displayed reduced JNK and p38 signaling, while NF-jB was activated to a normal level but with delayed kinetics compared to wildtype cells. TLR4-mediated IRF3 activation was intact in these cells. Comprehensive analysis of expression of LPS-inducible genes by microarray demonstrated that IRAK-4 KD cells were severely impaired in the expression of many pro-inflammatory genes, suggesting their dependence on IRAK-4 kinase activity. In contrast, the expression of a subset of LPS-induced genes of anti-viral response was not affected by IRAK-4 kinase deficiency. Additionally, we demonstrate that LPS-activated early expression and production of some cytokines, e.g., TNF-a, is partially induced in the absence of IRAK-4 kinase activity. This suggests that the partially unaffected TLR4-mediated signaling could still drive expression of these genes in early phases and that IRAK-4 kinase activity is important for a more sustained anti-bacterial response. IntroductionThe Toll-like receptor (TLR) family of molecules mediates innate immunity by recognizing specific pathogen-associated molecular patterns [1]. The TLR signaling pathways share common components with IL-1 receptor signaling. Upon ligand binding, the intracellular adaptor protein myeloid differentiation factor 88 (MyD88) interacts with the receptor via Toll/ IL-1 receptor (TIR) domains. This leads to recruitment of IL-1 receptor-associated kinase-4 (IRAK-4) and IRAK-1 and TNF-associated factor 6 (TRAF6) to the receptor complex [2,3]. As a consequence, IRAK-1 is phosphorylated [4,5], and later ubiquitinylated and degraded [6]. Hyperphosphorylated IRAK-1 and TRAF6 leave the receptor complex to further activate downstream IjB kinases (IKK) and mitogen-activated protein kinases (MAPK): p38 and Jun-N-terminal kinases (JNK) [7,8]. Subsequently, this triggers activation of transcription factors such as NF-jB and AP-1, which are involved in control of expression of many pro-inflammatory genes encoding cytokines, chemokines, adhesion molecules and proteolytic enzymes [9,10]. Among TLR, TLR4 is the receptor for lipopolysaccharide (LPS), a major cell wall component of Gramnegative bacteria [11]. In addition to the MyD88-dependent signaling pathway, TLR4 can also recruit another adaptor molecule, the TIR domain-containing adaptor inducing IFN-b (TRIF) [12]. This MyD88-independent TRIF-dependent pathway triggers activation of NF-jB, AP-1, as well as IFN regulatory factor 3 (IRF3) transcription factors [1,13]. IRF3 contributes to the expression of genes such as IFN-c-inducible protein 10 (IP-10/Cxcl10) and IFN-b, involved in anti-viral immune responses [14,15].Despite the fact that the essential role of IRAK-4...

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Differential induction of monocyte chemotactic protein-3 in mononuclear leukocytes and fibroblasts by interferon-α / β and interferon-γ reveals MCP-3 heterogeneity

Cited by 66 publications

References 19 publications

The CXC Chemokine GCP-2/CXCL6 Is Predominantly Induced in Mesenchymal Cells by Interleukin-1β and Is Down-Regulated by Interferon-γ: Comparison with Interleukin-8/CXCL8

The CXC Chemokine GCP-2/CXCL6 Is Predominantly Induced in Mesenchymal Cells by Interleukin-1β and Is Down-Regulated by Interferon-γ: Comparison with Interleukin-8/CXCL8

MCP‐3 (CCL7) delivered by parvovirus MVMp reduces tumorigenicity of mouse melanoma cells through activation of T lymphocytes and NK cells

IRAK‐4 kinase activity‐dependent and ‐independent regulation of lipopolysaccharide‐inducible genes

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