Toll-like receptor-4 and mitogen-activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome

Immunology. 2008 Sep;125(1):122-30. doi: 10.1111/j.1365-2567.2008.02827.x. Epub 2008 Mar 27.

Abstract

Atherosclerosis is an inflammatory disease in which dendritic cells have been suggested to play an essential role. The underlying signalling mechanisms are unknown thus far. The family of Toll-like receptors (TLRs) initiates innate immune responses, and Toll-like receptor-4 (TLR4) has been considered to be an important player in the initiation and progression of atherosclerotic disease. The highly conserved mitogen-activated protein kinase (MAPK) family is one of the major kinase families that regulate cells by transducing extracellular into cellular responses. Three important members of this family are the extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The aim of the study was to investigate the expression of TLR4 and MAPK families on dendritic cells (DC) in patients with coronary arteriosclerosis disease. We have examined the expression of TLR4 protein and mRNA by flow cytometry and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). In addition, the expression of MAPK family proteins have been determined by Western blot analysis. We examined the expression level of CD80 to value the maturation state of DC. We compared the levels of cytokines in DC in response to lipopolysaccharide (LPS). The results showed that the expression of TLR4 and MAPK families are increased in the patients with acute coronary syndrome (ACS), compared with it in the patients with stable angina and controls. DC in ACS are activated evaluated by its mature marker and cytokine secreting responding to LPS. We suggest that TLR4 and MAPK families maybe involved in activation of circulating DC of ACS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / immunology*
  • Angina Pectoris / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • MAP Kinase Signaling System / immunology*
  • Mitogen-Activated Protein Kinases / immunology
  • Mitogen-Activated Protein Kinases / metabolism
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*

Substances

  • Cytokines
  • RNA, Messenger
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Mitogen-Activated Protein Kinases