Limits...
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

Top 20 biological functions from a comparative gene enrichment analysis of IL27 and calprotectin-mediated gene expression. The biological function gene enrichment analysis was carried out by IPA and represents the z-score (activation ≥ 2).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4664814&req=5

fig2: Top 20 biological functions from a comparative gene enrichment analysis of IL27 and calprotectin-mediated gene expression. The biological function gene enrichment analysis was carried out by IPA and represents the z-score (activation ≥ 2).

Mentions: We next performed functional gene enrichment analyses using the Ingenuity Pathway Analysis (IPA) tool. The significantly regulated unique genes were merged for each stimulus. A core analysis was carried out and biological annotation enrichment was generated based on genes. The top 20 biological functions derived from calprotectin and IL27-regulated genes are shown in Figure 2. IL27-mediated gene expression showed that IL27 activated all of the presented top 20 biological functions, including, for example, inflammatory response and activation, stimulation, and migration of leukocytes (z-score ≥ 2). However, calprotectin only mediated the activation of 1 out of the 20 presented biological functions. This pathway analysis reveals that while IL27 appears to be involved in typical inflammatory functions, the activity of calprotectin is less obvious.


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)

Top 20 biological functions from a comparative gene enrichment analysis of IL27 and calprotectin-mediated gene expression. The biological function gene enrichment analysis was carried out by IPA and represents the z-score (activation ≥ 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Top 20 biological functions from a comparative gene enrichment analysis of IL27 and calprotectin-mediated gene expression. The biological function gene enrichment analysis was carried out by IPA and represents the z-score (activation ≥ 2).
Mentions: We next performed functional gene enrichment analyses using the Ingenuity Pathway Analysis (IPA) tool. The significantly regulated unique genes were merged for each stimulus. A core analysis was carried out and biological annotation enrichment was generated based on genes. The top 20 biological functions derived from calprotectin and IL27-regulated genes are shown in Figure 2. IL27-mediated gene expression showed that IL27 activated all of the presented top 20 biological functions, including, for example, inflammatory response and activation, stimulation, and migration of leukocytes (z-score ≥ 2). However, calprotectin only mediated the activation of 1 out of the 20 presented biological functions. This pathway analysis reveals that while IL27 appears to be involved in typical inflammatory functions, the activity of calprotectin is less obvious.

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