The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages

<p>Abstract</p> <p>Atherosclerosis is considered a chronic inflammatory disease in which monocytes and macrophages are critical. These cells express CD14, toll-like receptor (TLR) 2, and TLR4 on their surfaces, are activated by minimally modified low-density lipoprotein (mmLDL) and...

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Main Authors: Blanco-Favela Francisco, Madrid-Miller Alejandra, Tesoro-Cruz Emiliano, Montoya-Díaz Eduardo, Zenteno Edgar, Ledesma-Soto Yadira, Legorreta-Haquet Maria, Chávez-Rueda Karina, Chávez-Sánchez Luis
Format: Article
Language:English
Published: BMC 2010-10-01
Series:Lipids in Health and Disease
Online Access:http://www.lipidworld.com/content/9/1/117
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author Blanco-Favela Francisco
Madrid-Miller Alejandra
Tesoro-Cruz Emiliano
Montoya-Díaz Eduardo
Zenteno Edgar
Ledesma-Soto Yadira
Legorreta-Haquet Maria
Chávez-Rueda Karina
Chávez-Sánchez Luis
author_facet Blanco-Favela Francisco
Madrid-Miller Alejandra
Tesoro-Cruz Emiliano
Montoya-Díaz Eduardo
Zenteno Edgar
Ledesma-Soto Yadira
Legorreta-Haquet Maria
Chávez-Rueda Karina
Chávez-Sánchez Luis
author_sort Blanco-Favela Francisco
collection DOAJ
description <p>Abstract</p> <p>Atherosclerosis is considered a chronic inflammatory disease in which monocytes and macrophages are critical. These cells express CD14, toll-like receptor (TLR) 2, and TLR4 on their surfaces, are activated by minimally modified low-density lipoprotein (mmLDL) and are capable of secreting pro-inflammatory cytokines. The aim of this research was thus to demonstrate that the activation of CD14, TLR2, and TLR4 by mmLDL induces the secretion of cytokines.</p> <p>Methods</p> <p>Human monocytes and macrophages were incubated with monoclonal antibodies specific for CD14, TLR4, and TLR2 prior to stimulation with mmLDL. Cytokine secretion was then compared to that observed upon mmLDL stimulation in untreated cells.</p> <p>Results</p> <p>Stimulation with mmLDL induced the secretion of pro-inflammatory cytokines. Blocking CD14 in monocytes inhibited secretion of interleukin (IL)-1β (72%), IL-6 (58%) and IL-10 (63%), and blocking TLR4 inhibited secretion of IL-1β by 67%, IL-6 by 63% and IL-10 by 60%. Blocking both receptors inhibited secretion of IL-1β by 73%, IL-6 by 69% and IL-10 by 63%. Furthermore, blocking TLR2 inhibited secretion of IL-1β by 65%, IL-6 by 62% and IL-10 by 75%. In macrophages, we found similar results: blocking CD14 inhibited secretion of IL-1β by 59%, IL-6 by 52% and IL-10 by 65%; blocking TLR4 inhibited secretion of IL-1β by 53%, IL-6 by 63% and IL-10 by 61%; and blocking both receptors inhibited secretion of IL-1β by 69%, IL-6 by 67% and IL-10 by 65%. Blocking TLR2 in macrophages inhibited secretion of IL-1β by 57%, IL-6 by 40% and IL-10 by 72%.</p> <p>Conclusion</p> <p>Our study demonstrates that CD14, TLR4, and TLR2 participate in the immune response against mmLDL by inducing the production of pro-inflammatory cytokines in both monocytes and macrophages. These findings suggest that the activation of these receptors by mmLDL contributes to the inflammatory process of atherosclerosis.</p>
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spelling doaj.art-8aef1dabd8054bfea0f714c35a53fc6e2022-12-22T00:35:38ZengBMCLipids in Health and Disease1476-511X2010-10-019111710.1186/1476-511X-9-117The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophagesBlanco-Favela FranciscoMadrid-Miller AlejandraTesoro-Cruz EmilianoMontoya-Díaz EduardoZenteno EdgarLedesma-Soto YadiraLegorreta-Haquet MariaChávez-Rueda KarinaChávez-Sánchez Luis<p>Abstract</p> <p>Atherosclerosis is considered a chronic inflammatory disease in which monocytes and macrophages are critical. These cells express CD14, toll-like receptor (TLR) 2, and TLR4 on their surfaces, are activated by minimally modified low-density lipoprotein (mmLDL) and are capable of secreting pro-inflammatory cytokines. The aim of this research was thus to demonstrate that the activation of CD14, TLR2, and TLR4 by mmLDL induces the secretion of cytokines.</p> <p>Methods</p> <p>Human monocytes and macrophages were incubated with monoclonal antibodies specific for CD14, TLR4, and TLR2 prior to stimulation with mmLDL. Cytokine secretion was then compared to that observed upon mmLDL stimulation in untreated cells.</p> <p>Results</p> <p>Stimulation with mmLDL induced the secretion of pro-inflammatory cytokines. Blocking CD14 in monocytes inhibited secretion of interleukin (IL)-1β (72%), IL-6 (58%) and IL-10 (63%), and blocking TLR4 inhibited secretion of IL-1β by 67%, IL-6 by 63% and IL-10 by 60%. Blocking both receptors inhibited secretion of IL-1β by 73%, IL-6 by 69% and IL-10 by 63%. Furthermore, blocking TLR2 inhibited secretion of IL-1β by 65%, IL-6 by 62% and IL-10 by 75%. In macrophages, we found similar results: blocking CD14 inhibited secretion of IL-1β by 59%, IL-6 by 52% and IL-10 by 65%; blocking TLR4 inhibited secretion of IL-1β by 53%, IL-6 by 63% and IL-10 by 61%; and blocking both receptors inhibited secretion of IL-1β by 69%, IL-6 by 67% and IL-10 by 65%. Blocking TLR2 in macrophages inhibited secretion of IL-1β by 57%, IL-6 by 40% and IL-10 by 72%.</p> <p>Conclusion</p> <p>Our study demonstrates that CD14, TLR4, and TLR2 participate in the immune response against mmLDL by inducing the production of pro-inflammatory cytokines in both monocytes and macrophages. These findings suggest that the activation of these receptors by mmLDL contributes to the inflammatory process of atherosclerosis.</p>http://www.lipidworld.com/content/9/1/117
spellingShingle Blanco-Favela Francisco
Madrid-Miller Alejandra
Tesoro-Cruz Emiliano
Montoya-Díaz Eduardo
Zenteno Edgar
Ledesma-Soto Yadira
Legorreta-Haquet Maria
Chávez-Rueda Karina
Chávez-Sánchez Luis
The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages
Lipids in Health and Disease
title The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages
title_full The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages
title_fullStr The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages
title_full_unstemmed The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages
title_short The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages
title_sort activation of cd14 tlr4 and tlr2 by mmldl induces il 1β il 6 and il 10 secretion in human monocytes and macrophages
url http://www.lipidworld.com/content/9/1/117
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