Cross talk between smooth muscle cells and monocytes/activated monocytes via CX3CL1/CX3CR1 axis augments expression of pro-atherogenic molecules

Elena Dragomir Butoi*, Ana Maria Gan, Ileana Manduteanu, Daniela Stan, Manuela Calin, Monica Pirvulescu, Rory Ryan Koenen, Christian Weber, Maya Simionescu

*Corresponding author for this work

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In atherosclerotic lesions, fractalkine (CX3CL1) and its receptor (CX3CR1) expressed by smooth muscle cells (SMC) and monocytes/macrophages, mediate the heterotypic anchorage and chemotaxis of these cells. We questioned whether, during the close interaction of monocytes with SMC, the CX3CL1/CX3CR1 pair modulates the expression of pro-atherogenic molecules in these cells.SMC were co-cultured with monocytes or LPS-activated monocytes (18h) and then the cells were separated and individually investigated for the gene and protein expression of TNF?, IL-1?, IL-6, CX3CR1 and metalloproteinases (MMP-2, MMP-9). We found that SMC-monocyte interaction induced, in each cell type, an increased mRNA and protein expression of TNF?, IL-1?, IL-6, CX3CR1, MMP-2 and MMP-9. Blocking the binding of fractalkine to CX3CR1 (by pre-incubation of monocytes with anti-CX3CR1 or by CX3CR1 siRNA transfection) before cell co-culture decreased the production of TNF?, CX3CR1 and MMP-9. Monocyte-SMC interaction induced the phosphorylation of p38MAPK and activation of AP-1 transcription factor. Silencing the p65 (NF-kB subunit) inhibited the IL-1? and IL-6 and silencing c-jun inhibited the TNF?, CX3CR1 and MMP-9 induced by SMC-monocyte interaction.The cross-talk between SMC and monocytes augments the inflammatory response in both cell types as revealed by the increased expression of TNF?, IL-1?, IL-6, CX3CR1 and MMPs. Up-regulation of TNF?, CX3CR1 and MMP-9 is further increased upon interaction of SMC with activated monocytes and is dependent on fractalkine/CXRCR1 pair. These data imply that the fractalkine/CX3RCR1 axis may represent a therapeutic target to impede the inflammatory process associated with atherosclerosis.
Original languageEnglish
Pages (from-to)2026-2035
JournalBiochimica et Biophysica Acta-Molecular Cell Research
Issue number12
Publication statusPublished - Dec 2011


  • Smooth muscle cell
  • Monocyte
  • Fractalkine
  • CX3CR1
  • Inflammatory cytokine
  • Metalloproteinase

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