title: Procalcitonin induced cytotoxicity and apoptosis in mesangial cells: implications for septic renal injury.
abstract: OBJECTIVE
  Immuno-neutralization of procalcitonin (ProCT) has been shown to ameliorate experimental sepsis as well as the renal complications of this disease. Accordingly, we investigated the direct effect of ProCT on mesangial cells (MCs).
  
  
  METHODS
  Primary culture of murine MCs.
  
  
  METHODS
  ProCT (0.5, 1.0, 2.5, 5.0 ng/ml) for 2, 4, 6 h.
  
  
  METHODS
  MCs were exposed in vitro to ProCT. Expression levels of IL-6, iNOS and TNF-α were determined by real time RT-PCR, Inflammatory pathways, and a panel of cytokines and chemokines involved in the process were investigated by PCR array; apoptosis/viability were evaluated in a multiplex assay and actin cytoskeleton alterations were examined by immunofluorescence (IF).
  
  
  RESULTS
  ProCT caused an early elevation in both IL-6 and iNOS mRNA (2-4 h), and a later rise (6 h) in TNF-α mRNA. ProCT upregulated genes of proinflammatory pathways 5- to 24-fold compared to control. IF images revealed disruption of the actin cytoskeleton and retraction of cell bodies with loss of typical stellate or spindle shape phenotype. ProCT decreased MCs viability by 36 % compared to control cells and induced significant apoptosis.
  
  
  CONCLUSIONS
  ProCT has direct cytotoxic properties and may play a role in septic acute kidney injury that is independent of endotoxemia or hemodynamic alterations.
authors.affiliation: Nephrology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Araujo
authors.forename: Sonia Q
authors.initials: SQ
authors.lastname: Doi
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Palant
authors.forename: Eric S
authors.initials: ES
authors.lastname: Nylen
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Becker
mesh_terms: D000199:Actins / Q000378:metabolism; D058186:Acute Kidney Injury; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000235:genetics; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011498:Protein Precursors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000199:Actins; C000606590:Calca protein, mouse; D015850:Interleukin-6; D011498:Protein Precursors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C544013:alpha-smooth muscle actin, mouse; D002116:Calcitonin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015740:Calcitonin Gene-Related Peptide