IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein

Abstract Background Cytokines and macrophages play a central role in the development of atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with differential effects on innate immune cells. We investigated the effects of IL-17 on macrophage differentiation and foam cell formation and...

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Main Authors: María de la Paz Sánchez-Martínez, Francisco Blanco-Favela, Mónica Daniela Mora-Ruiz, Adriana Karina Chávez-Rueda, Mariela Bernabe-García, Luis Chávez-Sánchez
Format: Article
Language:English
Published: BMC 2017-10-01
Series:Lipids in Health and Disease
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12944-017-0588-1
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author María de la Paz Sánchez-Martínez
Francisco Blanco-Favela
Mónica Daniela Mora-Ruiz
Adriana Karina Chávez-Rueda
Mariela Bernabe-García
Luis Chávez-Sánchez
author_facet María de la Paz Sánchez-Martínez
Francisco Blanco-Favela
Mónica Daniela Mora-Ruiz
Adriana Karina Chávez-Rueda
Mariela Bernabe-García
Luis Chávez-Sánchez
author_sort María de la Paz Sánchez-Martínez
collection DOAJ
description Abstract Background Cytokines and macrophages play a central role in the development of atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with differential effects on innate immune cells. We investigated the effects of IL-17 on macrophage differentiation and foam cell formation and activation in response to oxidized low-density lipoprotein (oxLDL). Methods Human monocytes were treated with IL-17 to induce macrophage differentiation. As controls, human monocytes were differentiated into M1 macrophages (M1) or M2 macrophages (M2). Subsequently, we analyzed the expression levels of markers such as CD80, CD36 and Toll-like receptors (TLRs) as well as foam cell formation and cytokines in M1, M2 and macrophages differentiated with IL-17 with or without oxLDL. Results The expression of M1 or M2 markers or cytokines was not induced in macrophages differentiated with IL-17. Macrophages differentiated with IL-17 formed few foam cells, with an average proportion of 20%, and expressed 3 times as much TLR2 and 3.8 times as much TLR4 as M0 macrophages. Additionally, macrophages differentiated with IL-17 acquired inflammatory capacity in response to oxLDL through the expression of specific markers, such as CD80, which increased 18-times compared with macrophages differentiated with IL-17 alone, and secreted 1.3 times less tumor necrosis factor (TNF)-α than M1. Additionally, oxLDL increased the levels of CD80, CD86 and IL-6 by 5.7, 2.8 and 1.4 times in M1 compared with M1 in the absence of oxLDL. In M2, oxLDL induced increases in the secretion of IL-6 and TNF-α that were 1.9 times and 1.2 times smaller, respectively, than those observed in M1. Conclusion Our study demonstrates that differentiation of macrophages with IL-17 does not induce the expression of markers or cytokines characteristic of M1 or M2 and these macrophages form few foam cells; however, the expression of TLR is increased. Moreover, these macrophages acquire the inflammatory capacity as evidenced by the expression of costimulatory molecules and secretion of pro-inflammatory cytokines in response to oxLDL. These findings suggest that the activation of macrophages differentiated with IL-17 by oxLDL contributes to the inflammatory process of atherosclerosis.
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spelling doaj.art-2dba9d438b894a87ba75d133e7edfcfc2022-12-22T00:42:04ZengBMCLipids in Health and Disease1476-511X2017-10-011611910.1186/s12944-017-0588-1IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoproteinMaría de la Paz Sánchez-Martínez0Francisco Blanco-Favela1Mónica Daniela Mora-Ruiz2Adriana Karina Chávez-Rueda3Mariela Bernabe-García4Luis Chávez-Sánchez5Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialUnidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialUnidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialUnidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialUnidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialUnidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialAbstract Background Cytokines and macrophages play a central role in the development of atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with differential effects on innate immune cells. We investigated the effects of IL-17 on macrophage differentiation and foam cell formation and activation in response to oxidized low-density lipoprotein (oxLDL). Methods Human monocytes were treated with IL-17 to induce macrophage differentiation. As controls, human monocytes were differentiated into M1 macrophages (M1) or M2 macrophages (M2). Subsequently, we analyzed the expression levels of markers such as CD80, CD36 and Toll-like receptors (TLRs) as well as foam cell formation and cytokines in M1, M2 and macrophages differentiated with IL-17 with or without oxLDL. Results The expression of M1 or M2 markers or cytokines was not induced in macrophages differentiated with IL-17. Macrophages differentiated with IL-17 formed few foam cells, with an average proportion of 20%, and expressed 3 times as much TLR2 and 3.8 times as much TLR4 as M0 macrophages. Additionally, macrophages differentiated with IL-17 acquired inflammatory capacity in response to oxLDL through the expression of specific markers, such as CD80, which increased 18-times compared with macrophages differentiated with IL-17 alone, and secreted 1.3 times less tumor necrosis factor (TNF)-α than M1. Additionally, oxLDL increased the levels of CD80, CD86 and IL-6 by 5.7, 2.8 and 1.4 times in M1 compared with M1 in the absence of oxLDL. In M2, oxLDL induced increases in the secretion of IL-6 and TNF-α that were 1.9 times and 1.2 times smaller, respectively, than those observed in M1. Conclusion Our study demonstrates that differentiation of macrophages with IL-17 does not induce the expression of markers or cytokines characteristic of M1 or M2 and these macrophages form few foam cells; however, the expression of TLR is increased. Moreover, these macrophages acquire the inflammatory capacity as evidenced by the expression of costimulatory molecules and secretion of pro-inflammatory cytokines in response to oxLDL. These findings suggest that the activation of macrophages differentiated with IL-17 by oxLDL contributes to the inflammatory process of atherosclerosis.http://link.springer.com/article/10.1186/s12944-017-0588-1Interleukin-17MacrophagesOxidized-low density lipoprotein
spellingShingle María de la Paz Sánchez-Martínez
Francisco Blanco-Favela
Mónica Daniela Mora-Ruiz
Adriana Karina Chávez-Rueda
Mariela Bernabe-García
Luis Chávez-Sánchez
IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein
Lipids in Health and Disease
Interleukin-17
Macrophages
Oxidized-low density lipoprotein
title IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein
title_full IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein
title_fullStr IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein
title_full_unstemmed IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein
title_short IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein
title_sort il 17 differentiated macrophages secrete pro inflammatory cytokines in response to oxidized low density lipoprotein
topic Interleukin-17
Macrophages
Oxidized-low density lipoprotein
url http://link.springer.com/article/10.1186/s12944-017-0588-1
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