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...
Main Authors: | , , , , , , , , |
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Format: | Article |
Language: | English |
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BMC
2010-10-01
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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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language | English |
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series | Lipids in Health and Disease |
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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