title: Acrolein-induced inflammatory signaling in vascular smooth muscle cells requires activation of serum response factor (SRF) and NFκB.
abstract: BACKGROUND
  Modulation of inflammatory signaling has been elucidated in several disease models. Acrolein, an environmental pollutant, has been linked to diseases such as atherosclerosis and to the inflammatory process involving nuclear factor κB (NFκB). Serum response factor (SRF), a transcription factor, regulates cell development, differentiation and proliferation through signaling molecules such as extracellular signal-regulated kinase 1/2 (ERK1/2) and CD36. We hypothesized that acrolein toxicity involves SRF in the process of activating NFκB and may involve CD36/ERK1/2.
  
  
  METHODS
  Vascular smooth muscle cells (VSMCs) were exposed to acrolein (0.5 μg/mL) in the presence or absence of 10 nM QNZ (NFκB inhibitor), 300 nM CCG1423 (SRF inhibitor) and 50 μM PD98059 (ERK1/2 inhibitor). Protein and RNA were isolated. Changes in expression were determined by Western blot and polymerase chain reaction (PCR) array.
  
  
  RESULTS
  Subtoxic doses of acrolein increased ERK1/2, SRF and NFκB protein expression, whereas CD36 expression was unchanged. Increase in NFκB expression was accompanied by an increase in activity. ERK1/2 inhibition only blunted SRF expression. SRF inhibition blunted NFκB expression but not that of ERK1/2. CD36 expression was unchanged in the presence of either inhibitor. PCR array analysis indicated up-regulation of nine genes (>4- to 50-fold) and down-regulation of six genes (>4- to 12-fold) involved in inflammatory signaling.
  
  
  CONCLUSIONS
  We propose that SRF is required in acrolein activation of NFκB and is ERK1/2 dependent.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Newaz
authors.forename: Zivar
authors.initials: Z
authors.lastname: Yousefipour
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D051381:Rats; D026362:Serum Response Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*
chemical_list: D004785:Environmental Pollutants; D016328:NF-kappa B; D026362:Serum Response Factor; D000171:Acrolein