Synergistic effect of PGD2 via prostanoid DP receptor on TNF-α-induced production of MCP-1 and IL-8 in human monocytic THP-1 cells

Hirano, Yuka; Shichijo, Michitaka; Deguchi, Masashi; Nagira, Morio; Suzuki, Noriko; Nishitani, Yoshinori; Hattori, Masatomo; Arimura, Akinori

doi:10.1016/j.ejphar.2007.01.003

Cited by 20 publications

(12 citation statements)

References 39 publications

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“…MCP-1 recruits immune cells to sites of tissue injury and infection, whereas IL-1␤ is a potent mediator of the inflammatory response. Induction of MCP-1 and IL-1␤ is induced largely or entirely through TNFR1 and is effected by activation of diverse signaling pathways and transcription factors (57)(58)(59)(60)(61)(62). Consistent with the pleiotropic mechanisms through which CCL2/MCP-1 and IL-1␤ can be induced, and the demonstration that c-Src and Jak2 are used by TNFR1 to engage diverse signaling pathways, we found that PP2 and AG490 each inhibited expression of these gene products.…”

Section: Discussionsupporting

confidence: 54%

Type 1 TNF Receptor Forms a Complex with and Uses Jak2 and c-Src to Selectively Engage Signaling Pathways That Regulate Transcription Factor Activity

Pincheira

Castro

Özeş

et al. 2008

The Journal of Immunology

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The type 1 TNFR (TNFR1) contains a death domain through which it interacts with other death-domain proteins to promote cellular responses. However, signaling through death-domain proteins does not explain how TNFR1 induces the tyrosine phosphorylation of intracellular proteins, which are important to cellular responses induced by TNFR1. In this study, we show that TNFR1 associates with Jak2, c-Src, and PI3K in various cell types. Jak2 and c-Src constitutively associate with and are constitutively active in the TNFR1 complex. Stimulation with TNF induces a time-dependent change in the level of Jak2, c-Src, and PI3K associated with TNFR1. The tyrosine kinase activity of the complex varies with the level of tyrosine kinase associated with TNFR1. TNFR1/c-Src plays a role in activating Akt, but not JNK or p38 MAPK, whereas TNFR1/Jak2 plays a role in activating p38 MAPK, JNK, and Akt. TNFR1/c-Src, but not TNFR1/Jak2, plays an obligate role in the activation of NF-κB by TNF, whereas TNFR1/Jak2, but not TNFR1/c-Src, plays an obligate role in the activation of STAT3. Activation of TNFR1 increased the expression of vascular endothelial growth factor, p21WAF1/CIP1, and manganese superoxide dismutase in MCF7 breast cancer cells, and increased the expression of CCl2/MCP-1 and IL-1β in THP-1 macrophages. Inhibitors of Jak2 and c-Src impaired the induction of each of these target proteins. These observations show that TNFR1 associates with and uses nonreceptor tyrosine kinases to engage signaling pathways, activate transcription factors, and modulate gene expression in cells.

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Section: Discussionsupporting

confidence: 54%

Type 1 TNF Receptor Forms a Complex with and Uses Jak2 and c-Src to Selectively Engage Signaling Pathways That Regulate Transcription Factor Activity

Pincheira

Castro

Özeş

et al. 2008

The Journal of Immunology

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“…Chronic leg ulcers are associated with elevated expression of pro-inflammatory cytokines, like TNF-α and MIF, compared to acute wounds [39]–[41]. These cytokines promote the production of more pro-inflammatory cytokines [42], [43], up-regulate the synthesis of matrix metalloproteinases and serine proteases [24], [42], [44] and activate the reactive oxygen generating system [45], [46]. Together, these pro-inflammatory actions result in extracellular matrix destruction [47]–[49] and inactivation of growth factors and protease inhibitors [44], [50]–[52].…”

Section: Discussionmentioning

confidence: 99%

Maggot Secretions Skew Monocyte-Macrophage Differentiation Away from a Pro-Inflammatory to a Pro-Angiogenic Type

2009

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BackgroundMaggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Earlier we reported maggot secretions to inhibit pro-inflammatory responses of human monocytes. The aim of this study was to investigate the effect of maggot secretions on the differentiation of monocytes into pro-inflammatory (MØ-1) and anti-inflammatory/pro-angiogenic macrophages (MØ-2) as these cells play a central role in wound healing.Methodology/Principal FindingsFreshly isolated monocytes were incubated with secretions and GM-CSF or M-CSF for 6 days and then stimulated with LPS or LTA for 18 h. The expression of cell surface molecules and the levels of cytokines, chemokines and growth factors in supernatants were measured. Our results showed secretions to affect monocyte-macrophage differentiation leading to MØ-1 with a partial MØ-2-like morphology but lacking CD163, which is characteristic for MØ-2. In response to LPS or LTA, secretions-differentiated MØ-1 produced less pro-inflammatory cytokines (TNF-α, IL-12p40 and MIF) than control cells. Similar results were observed for MØ-2 when stimulated with low concentrations of LPS. Furthermore, secretions dose-dependently led to MØ-1 and MØ-2 characterized by an altered chemokine production. Secretions led to MØ-2, but not MØ-1, producing enhanced levels of the growth factors bFGF and VEGF, as compared to control cells. The expression of cell-surface receptors involved in LPS/LTA was enhanced by secretions, that of CD86 and HLA-DR down-regulated, while receptors involved in phagocytosis remained largely unaffected.ConclusionsMaggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.

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“…For example, Hirano et al [88] recently examined the effects of PGD 2 on the production of monocyte chemoattractant protein (MCP)-1 and IL-8 by a human monocytic cell line, THP-1. Single activation of prostanoid DP receptor hardly produced any cytokines or chemokines.…”

Section: Nonhematopoietic Cells In Asthmamentioning

confidence: 98%

Prostaglandin D2 Receptors DP and CRTH2 in the Pathogenesis of Asthma

Arima

Fukuda²

2008

CMM

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Prostaglandin D2 (PGD2) is a major prostanoid produced mainly by mast cells in allergic diseases, including bronchial asthma. However, its role in the pathogenesis of asthma remains unclear. PGD2-induced vasodilatation and increased permeability are well-known classical effects that may facilitate transendothelial migration of inflammatory cells, such as eosinophils, mast cells, lymphocytes, and monocytes in allergic inflammation. These effects are initiated via a PGD2 receptor, D prostanoid receptor (DP), and are referred to as DP-mediated vasodilation-extravasation. Recently, novel functions of DP have been identified. Furthermore, a novel and different receptor of PGD2, CRTH2, has been discovered. To date, DP and CRTH2 have been shown to be major PGD(2)-related receptors that have pivotal roles in mediating allergic diseases by effects such as directly regulating the migration of inflammatory cells and controlling the production of cytokines and lipid mediators. Available evidence suggests that CRTH2 and DP may collaborate in allergic inflammation. This review focuses on the novel roles of DP and CRTH2 in the initiation and maintenance of allergy.

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Synergistic effect of PGD2 via prostanoid DP receptor on TNF-α-induced production of MCP-1 and IL-8 in human monocytic THP-1 cells

Cited by 20 publications

References 39 publications

Type 1 TNF Receptor Forms a Complex with and Uses Jak2 and c-Src to Selectively Engage Signaling Pathways That Regulate Transcription Factor Activity

Type 1 TNF Receptor Forms a Complex with and Uses Jak2 and c-Src to Selectively Engage Signaling Pathways That Regulate Transcription Factor Activity

Maggot Secretions Skew Monocyte-Macrophage Differentiation Away from a Pro-Inflammatory to a Pro-Angiogenic Type

Prostaglandin D2 Receptors DP and CRTH2 in the Pathogenesis of Asthma

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