Ceramide-enriched LDL induces cytokine release through TLR4 and CD14 in monocytes. Similarities with electronegative LDL

Montserrat Estruch, Jose Luis Sánchez-Quesada, Jordi Ordóñez-Llanos, Sonia Benítez

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Introduction: In vitro ceramide-enriched LDL (CER-LDL) reproduces most of the properties of electronegative LDL (LDL(-)), a heterogeneous subfraction of LDL found in plasma. LDL(-) comprises several modifications of LDL and has an increased content in ceramide (CER). It promotes cytokine release in monocytes through CD14 and TLR4. CER-LDL also induces cytokine release in these cells but the mechanism is unknown. Aim: To evaluate TLR4 andCD14 as the putative receptors involved in cytokine release induced by CER-LDL. Methods: CER-LDL was obtained by incubating native LDL with CER-enriched liposomes. CER content in CER-LDL was assessed by thin layer chromatography of lipid extracts. CER-LDL and LDL(-) were incubated for 20. h with human monocytes in the presence or absence of a TLR4 signaling inhibitor. Both LDLs were also incubated with two human monocytic cell lines, normal and THP1 overexpressing CD14 (THP1-CD14) cells. The release of IL-6, IL-10 and MCP-1 was evaluated by ELISA in culture medium. Results: The release of IL-6, IL-10 and MCP-1 induced by CER-LDL in monocytes was inhibited by VIPER (90% inhibition), a specific TLR4 inhibitor. The cytokine release induced by CER-LDL was negligible in THP1, cells presenting a very low CD14 expression. In contrast, the induction of cytokine release in THP1-CD14 was high and dependent on the CER content in LDL. Conclusion: CER-LDL induces IL-6, IL-10 and MCP-1 release through the activation of CD14 and TLR4 in monocytes, reproducing the behavior of LDL(-). The increased content of CER in LDL(-) is then related to the inflammatory action of LDL(-). © 2013 Sociedad Española de Arteriosclerosis.
Original languageEnglish
Pages (from-to)131-137
JournalClinica e Investigacion en Arteriosclerosis
Volume26
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • CD14
  • Ceramide
  • Cytokines
  • Electronegative LDL
  • Monocytes
  • TLR4

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