title: p-cresol but not p-cresyl sulfate stimulate MCP-1 production via NF-κB p65 in human vascular smooth muscle cells.
abstract: BACKGROUND
  p-cresol (PC) and p-cresyl sulfate (PCS) are responsible for many of the uremia clinical consequences, such as atherosclerosis in Chronic Kidney Disease (CKD) patients.
  
  
  OBJECTIVE
  We investigate the in vitro impact of PC and PCS on monocyte chemoattractant protein-1 (MCP-1) expression via NF-kappa B (NF-κB) p65 in VSMC.
  
  
  METHODS
  PCS was synthesized by PC sulfatation. VSMC were extracted by enzymatic digestion of umbilical cord vein and characterized by immunofluorescence against α-actin antibody. The cells were treated with PC and PCS at their normal (n), uremic (u) and maximum uremic concentrations (m). Cell viability was assessed by MTT. MCP-1 expression was investigated by ELISA in cells supernatants after toxins treatment with or without the NF-κB p65 inhibitor.
  
  
  RESULTS
  There was no significant difference in cell viability after toxins treatment for all concentrations tested. There was a significant increase in MCP-1 expression in cells treated with PCu and PCm (p < 0.001) and PCSn, PCSu and PCSm (p < 0.001), compared with the control. When VSMC were treated with the NF-κB p65 inhibitor plus PCu and PCm, there was a significant decrease in MCP-1 production (p < 0.005). This effect was not observed with PCS.
  
  
  CONCLUSIONS
  VSMC are involved in atherosclerosis lesion formation and production of MCP-1, which contributes to the inflammatory response initiation. Our results suggest that PC mediates MCP-1 production in VSMC, probably through NF-κB p65 pathway, although we hypothesize that PCS acts through a different subunit pathway since NF-κB p65 inhibitor was not able to inhibit MCP-1 production.
authors.affiliation: Universidade Federal do Paraná, Brazil.
authors.forename: Rayana Ariane Pereira
authors.initials: RA
authors.lastname: Maciel
authors.affiliation: Universidade Federal do Paraná, Brazil.
authors.forename: Lisienny Campoli Tono
authors.initials: LC
authors.lastname: Rempel
authors.affiliation: Universidade Federal do Paraná, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Bosquetti
authors.affiliation: Universidade Federal do Paraná, Brazil.
authors.forename: Alessandra Becker
authors.initials: AB
authors.lastname: Finco
authors.affiliation: Universidade Católica do Paraná, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pecoits-Filho
authors.affiliation: Universidade Federal do Paraná, Brazil.
authors.forename: Wesley Mauricio de
authors.initials: WM
authors.lastname: Souza
authors.affiliation: Universidade Federal do Paraná, Brazil.
authors.forename: Andréa Emilia Marques
authors.initials: AE
authors.lastname: Stinghen
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000187:drug effects*; D003408:Cresols / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000502:physiology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003408:Cresols; D013463:Sulfuric Acid Esters; D051996:Transcription Factor RelA; C032538:4-cresol; C408690:4-cresol sulfate