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Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells.

Dorosz SA, Ginolhac A, Kähne T, Naumann M, Sauter T, Salsmann A, Bueb JL - Mediators Inflamm. (2015)

Bottom Line: However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification.A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11.Furthermore, we showed evidence for STAT1 involvement in this process.

View Article: PubMed Central - PubMed

Affiliation: Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, Luxembourg.

ABSTRACT
An underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several key players such as IL6, TNFα, or the damage associated molecular pattern molecule (DAMP) calprotectin are now well identified. However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification. Therefore, we examined the inflammatory impact of IL27 on primary endothelial cells and the potentially modulatory effect of calprotectin on both transcriptome and proteome levels. A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11. Calprotectin time-dependent downregulatory effects were observed on IL27-induced IL15 and CXCL10 gene expression. A mass spectrometry-based approach of IL27 ± calprotectin cell stimulation enlightened a calprotectin modulatory role in the expression of 28 proteins, mostly involved in the mechanism of leukocyte transmigration. Furthermore, we showed evidence for STAT1 involvement in this process. Our findings provide new evidence about the IL27-dependent proinflammatory signaling which may be under the control of calprotectin and highlight the need for further investigations on molecules which might have antiatherosclerotic functions.

No MeSH data available.


Related in: MedlinePlus

Hypothetical model of the calprotectin modulatory effects on IL27-mediated gene and protein expression based on our experimental results and literature data. GBP1, guanylate binding protein 1; NID1, nidogen-1; PECAM1, platelet endothelial cell adhesion molecule; TPM1, tropomyosin 1.
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fig8: Hypothetical model of the calprotectin modulatory effects on IL27-mediated gene and protein expression based on our experimental results and literature data. GBP1, guanylate binding protein 1; NID1, nidogen-1; PECAM1, platelet endothelial cell adhesion molecule; TPM1, tropomyosin 1.

Mentions: Regarding our results, we therefore propose a model of a calprotectin reducing effect on IL27-mediated inflammation of the vascular endothelium in the context of atherosclerosis. Figure 8 describes the possible mechanism of IL27-induced vascular inflammation and the potential atheroprotective role of calprotectin in this context. IL27 induced the secretion of the chemokines CXCL10 and CXCL11 which are known to attract monocytes as well as T cells. In more detail, CXCL10 and CXCL11 mainly recruit CD4 or CD8 T cells, which also represent the main T cell subsets found in atherosclerotic plaques [58–60]. CXCL10 and CXCL11 can bind via their cognate receptor CXCR3 which is highly expressed on monocytes, T cells, and NK cells [61]. In the atherosclerotic context, endothelial cells do not express CXCR3 but use a very defined system [62]. CXC chemokines such as CXCL10 and CXCL11 can also bind, for example, to heparan sulfate proteoglycans, which are present at the cell surface of endothelial cells. This binding of CXCL10 and CXCL11 can facilitate the rolling of monocytes and T cells on the vascular endothelium [62, 63]. Furthermore, it can facilitate the adhesion to other proteins such as the transpresented IL15 at the surface of endothelial cells. T cells and monocytes express the counterparts IL2Rα and IL2R for IL15R to form the tridimeric IL15 receptor [64]. Independent studies have shown the transendothelial migration of T cells and monocytes through IL15 expression on endothelial cells [64, 65].


Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells.

Dorosz SA, Ginolhac A, Kähne T, Naumann M, Sauter T, Salsmann A, Bueb JL - Mediators Inflamm. (2015)

Hypothetical model of the calprotectin modulatory effects on IL27-mediated gene and protein expression based on our experimental results and literature data. GBP1, guanylate binding protein 1; NID1, nidogen-1; PECAM1, platelet endothelial cell adhesion molecule; TPM1, tropomyosin 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4664814&req=5

fig8: Hypothetical model of the calprotectin modulatory effects on IL27-mediated gene and protein expression based on our experimental results and literature data. GBP1, guanylate binding protein 1; NID1, nidogen-1; PECAM1, platelet endothelial cell adhesion molecule; TPM1, tropomyosin 1.
Mentions: Regarding our results, we therefore propose a model of a calprotectin reducing effect on IL27-mediated inflammation of the vascular endothelium in the context of atherosclerosis. Figure 8 describes the possible mechanism of IL27-induced vascular inflammation and the potential atheroprotective role of calprotectin in this context. IL27 induced the secretion of the chemokines CXCL10 and CXCL11 which are known to attract monocytes as well as T cells. In more detail, CXCL10 and CXCL11 mainly recruit CD4 or CD8 T cells, which also represent the main T cell subsets found in atherosclerotic plaques [58–60]. CXCL10 and CXCL11 can bind via their cognate receptor CXCR3 which is highly expressed on monocytes, T cells, and NK cells [61]. In the atherosclerotic context, endothelial cells do not express CXCR3 but use a very defined system [62]. CXC chemokines such as CXCL10 and CXCL11 can also bind, for example, to heparan sulfate proteoglycans, which are present at the cell surface of endothelial cells. This binding of CXCL10 and CXCL11 can facilitate the rolling of monocytes and T cells on the vascular endothelium [62, 63]. Furthermore, it can facilitate the adhesion to other proteins such as the transpresented IL15 at the surface of endothelial cells. T cells and monocytes express the counterparts IL2Rα and IL2R for IL15R to form the tridimeric IL15 receptor [64]. Independent studies have shown the transendothelial migration of T cells and monocytes through IL15 expression on endothelial cells [64, 65].

Bottom Line: However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification.A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11.Furthermore, we showed evidence for STAT1 involvement in this process.

View Article: PubMed Central - PubMed

Affiliation: Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, Luxembourg.

ABSTRACT
An underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several key players such as IL6, TNFα, or the damage associated molecular pattern molecule (DAMP) calprotectin are now well identified. However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification. Therefore, we examined the inflammatory impact of IL27 on primary endothelial cells and the potentially modulatory effect of calprotectin on both transcriptome and proteome levels. A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11. Calprotectin time-dependent downregulatory effects were observed on IL27-induced IL15 and CXCL10 gene expression. A mass spectrometry-based approach of IL27 ± calprotectin cell stimulation enlightened a calprotectin modulatory role in the expression of 28 proteins, mostly involved in the mechanism of leukocyte transmigration. Furthermore, we showed evidence for STAT1 involvement in this process. Our findings provide new evidence about the IL27-dependent proinflammatory signaling which may be under the control of calprotectin and highlight the need for further investigations on molecules which might have antiatherosclerotic functions.

No MeSH data available.


Related in: MedlinePlus