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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

Effects of TNFα, calprotectin, and TNFα/calprotectin cotreatment on gene expression. Relative mRNA levels of IL7, IL15, CXCL10, and CXCL11 of TNFα (2 ng/mL) ± calprotectin (1 μg/mL)-stimulated HUVECs for 3, 6, 12, and 24 h are represented as mean ± SEM (n = 3). Indicated p values are corresponding to significant differences between TNFα and TNFα + calprotectin: ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.
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fig4: Effects of TNFα, calprotectin, and TNFα/calprotectin cotreatment on gene expression. Relative mRNA levels of IL7, IL15, CXCL10, and CXCL11 of TNFα (2 ng/mL) ± calprotectin (1 μg/mL)-stimulated HUVECs for 3, 6, 12, and 24 h are represented as mean ± SEM (n = 3). Indicated p values are corresponding to significant differences between TNFα and TNFα + calprotectin: ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.

Mentions: In order to confirm the proinflammatory activity for IL27 and the calprotectin modulatory effects, the HUVECs were stimulated with TNFα (2 ng/mL) ± calprotectin (1 μg/mL) for 3, 6, 12, and 24 h, and the gene expression of IL7, IL15, CXCL10, and CXCL11 was analysed by RT-qPCR (Figure 4). We observed similar TNFα-mediated gene upregulation of IL7, IL15, CXCL10, and CXCL11. Furthermore, calprotectin induced downregulatory effects on TNFα-mediated gene expression of IL7, IL15, and CXCL10, hence validating our previous findings and emphasizing the IL15- and CXCL10-specific regulatory role of calprotectin.


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)

Effects of TNFα, calprotectin, and TNFα/calprotectin cotreatment on gene expression. Relative mRNA levels of IL7, IL15, CXCL10, and CXCL11 of TNFα (2 ng/mL) ± calprotectin (1 μg/mL)-stimulated HUVECs for 3, 6, 12, and 24 h are represented as mean ± SEM (n = 3). Indicated p values are corresponding to significant differences between TNFα and TNFα + calprotectin: ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Effects of TNFα, calprotectin, and TNFα/calprotectin cotreatment on gene expression. Relative mRNA levels of IL7, IL15, CXCL10, and CXCL11 of TNFα (2 ng/mL) ± calprotectin (1 μg/mL)-stimulated HUVECs for 3, 6, 12, and 24 h are represented as mean ± SEM (n = 3). Indicated p values are corresponding to significant differences between TNFα and TNFα + calprotectin: ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.
Mentions: In order to confirm the proinflammatory activity for IL27 and the calprotectin modulatory effects, the HUVECs were stimulated with TNFα (2 ng/mL) ± calprotectin (1 μg/mL) for 3, 6, 12, and 24 h, and the gene expression of IL7, IL15, CXCL10, and CXCL11 was analysed by RT-qPCR (Figure 4). We observed similar TNFα-mediated gene upregulation of IL7, IL15, CXCL10, and CXCL11. Furthermore, calprotectin induced downregulatory effects on TNFα-mediated gene expression of IL7, IL15, and CXCL10, hence validating our previous findings and emphasizing the IL15- and CXCL10-specific regulatory role of calprotectin.

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