title: Cross talk between smooth muscle cells and monocytes/activated monocytes via CX3CL1/CX3CR1 axis augments expression of pro-atherogenic molecules.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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 TNFα, IL-1β, 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 TNFα, IL-1β, 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 TNFα, 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-1β and IL-6 and silencing c-jun inhibited the TNFα, CX3CR1 and MMP-9 induced by SMC-monocyte interaction.
  
  
  CONCLUSIONS
  The cross-talk between SMC and monocytes augments the inflammatory response in both cell types as revealed by the increased expression of TNFα, IL-1β, IL-6, CX3CR1 and MMPs. Up-regulation of TNFα, 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.
authors: Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania. elena.dragomir@icbp.ro
authors: Elena Dragomir
authors: ED
authors: Butoi
authors: Ana Maria
authors: AM
authors: Gan
authors: Ileana
authors: I
authors: Manduteanu
authors: Daniela
authors: D
authors: Stan
authors: Manuela
authors: M
authors: Calin
authors: Monica
authors: M
authors: Pirvulescu
authors: Rory Ryan
authors: RR
authors: Koenen
authors: Christian
authors: C
authors: Weber
authors: Maya
authors: M
authors: Simionescu
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9