title: Determination of protein phosphatase type 2A in monocytes from multiple trauma patients: a potential biomarker for sepsis.
abstract: BACKGROUND
  Protein phosphatase type 2A (PP2A) can downregulate c-Jun N-terminal kinase (JNK) expression in monocytes stimulated by lipopolysaccharide. However, this effect has not been evaluated in patients with sepsis. We sought to determine whether PP2A/JNK pathway is involved in sepsis and whether PP2A expression can be associated with patient outcome.
  
  
  METHODS
  We measured PP2A, c-Jun, and JNK protein as well as PP2A and c-Jun messenger RNA in monocytes from trauma patients with (n = 24) or without (n = 22) sepsis 1 and 7 d after major trauma and from healthy volunteers (n = 15) by Western blotting and quantitative real-time polymerase chain reaction. Patient outcomes, including intensive care unit length of stay, Sequential Organ Failure Assessment score, and Multiple Organ Dysfunction score were compared between groups. Correlations between PP2A and c-Jun/JNK expression as well as patient outcomes were analyzed. Receiver operating characteristic analysis was performed to determine the diagnostic efficiency of PP2A for sepsis.
  
  
  RESULTS
  PP2A protein and messenger RNA expression were significantly higher in septic patients compared with nonseptic patients or healthy volunteers. Conversely, the expressions of JNK and c-Jun were significantly reduced in septic patients and correlated inversely with PP2A expression. Furthermore, PP2A expression was positively associated with LOS, Sequential Organ Failure Assessment and Multiple Organ Dysfunction score at day 1 and day 7. Receiver operating characteristic curve yielded a high sensitivity (87.5%) of PP2A in discriminating septic versus nonseptic patients.
  
  
  CONCLUSIONS
  PP2A may serve as a negative regulator of the JNK pathway and a biomarker for sepsis.
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Hui-xing
authors.initials: HX
authors.lastname: Yi
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: Jing-yu
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ru-bin
authors.initials: RB
authors.lastname: Luo
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Shou-yin
authors.initials: SY
authors.lastname: Jiang
authors.affiliation: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: z2emergent@gmail.com.
authors.forename: Jian-an
authors.initials: JA
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D064368:Healthy Volunteers; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology* / Q000473:pathology; D011446:Prospective Studies; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D012372:ROC Curve; D018805:Sepsis / Q000201:enzymology* / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D054648:Protein Phosphatase 2
keywords: Biomarker; C-Jun; JNK; Phosphatase type 2A; Sepsis