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

• Published in: Lipids in health and disease Vol. 9; p. 117
• Main Authors: Chávez-Sánchez, Luis, Chávez-Rueda, Karina, Legorreta-Haquet, Maria Victoria, Zenteno, Edgar, Ledesma-Soto, Yadira, Montoya-Díaz, Eduardo, Tesoro-Cruz, Emiliano, Madrid-Miller, Alejandra, Blanco-Favela, Francisco
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 14-10-2010; BioMed Central
• Subjects: Atherosclerosis; Experiments; Interleukins; Lipoproteins; Low density lipoproteins; Macrophages; Medical research; Physiological aspects; Proteins; Studies; Toll-like receptors; Mexico
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/1476-511X-9-117

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. Methods 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. Results Stimulation with mmLDL induced the secretion of pro-inflammatory cytokines. Blocking CD14 in monocytes inhibited secretion of interleukin (IL)-1[beta] (72%), IL-6 (58%) and IL-10 (63%), and blocking TLR4 inhibited secretion of IL-1[beta] by 67%, IL-6 by 63% and IL-10 by 60%. Blocking both receptors inhibited secretion of IL-1[beta] by 73%, IL-6 by 69% and IL-10 by 63%. Furthermore, blocking TLR2 inhibited secretion of IL-1[beta] by 65%, IL-6 by 62% and IL-10 by 75%. In macrophages, we found similar results: blocking CD14 inhibited secretion of IL-1[beta] by 59%, IL-6 by 52% and IL-10 by 65%; blocking TLR4 inhibited secretion of IL-1[beta] by 53%, IL-6 by 63% and IL-10 by 61%; and blocking both receptors inhibited secretion of IL-1[beta] by 69%, IL-6 by 67% and IL-10 by 65%. Blocking TLR2 in macrophages inhibited secretion of IL-1[beta] by 57%, IL-6 by 40% and IL-10 by 72%. Conclusion 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.