title: The SHP-1 expression is associated with cytokines and psychopathological status in unmedicated first episode schizophrenia patients.
abstract: BACKGROUND
  Recent lines of research have boosted awareness of the immunological facets of schizophrenia. However, associations with protein tyrosine phosphatase regulators have never been reported. The aim of our study was to investigate the expression and promoter status methylation of phosphatase SHP-1, a key negative regulator of the inflammatory process, in Peripheral blood mononuclear cells (PBMCs) of Schizophrenic patients.
  
  
  METHODS
  We enrolled fifty-four (28 men and 26 women) unmedicated first episode subjects (SC) who met DSM-IV and thirty-eight (22 men and 16 women) healthy controls (HC). The SC psychopathological status was assessed using the Positive and Negative Syndrome Scale. We evaluated SHP-1 expression by Quantitative Real-time PCR (qPCR) and Western blotting (WB) methods and promoter status methylation through PCR bisulfate. IKK/NFkB signaling was detected by WB, and medium and plasma levels of pro-inflammatory cytokines (IL-1β, IL-2, and TNF-α) by the ELISA method. SHP-1 was silenced by treating cells with specific siRNA.
  
  
  RESULTS
  We found a significantly lower level of SHP-1 gene expression in PBMCs from SC vs. HC, consistently with which the promoter region analyzed presented significant hypermethylation. Silencing of SHP-1 expression induced higher activation of IKK/NF-kB signaling and pro-inflammatory cytokine production in ex vivo PBMCs from both SC and HC. Linear regression among patients generated a model in which SHP-1 expression explained 30% of the clinical negative symptom variance (adjusted R(2)=0.30, ANOVA p<0.001).
  
  
  CONCLUSIONS
  Our findings are the first to suggest that impairment of SHP-1 expression is involved in the physiopathology of schizophrenia, opening fruitful new avenues for ameliorating treatment at least of negative symptoms.
authors.affiliation: Department of Psychological, Humanistic and Territorial Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pesce
authors.affiliation: Department of Medicine and Science of Aging, University "G. D'Annunzio", Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferrone
authors.affiliation: Department of Psychological, Humanistic and Territorial Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rizzuto
authors.affiliation: Department of Psychological, Humanistic and Territorial Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tatangelo
authors.affiliation: Department of Psychological, Humanistic and Territorial Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Iezzi
authors.affiliation: Department of Medicine and Science of Aging, University "G. D'Annunzio", Chieti, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ladu
authors.affiliation: Department of Medicine and Science of Aging, University "G. D'Annunzio", Chieti, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Franceschelli
authors.affiliation: Department of Medicine and Science of Aging, University "G. D'Annunzio", Chieti, Italy. Electronic address: l.speranza@unich.it.
authors.forename: L
authors.initials: L
authors.lastname: Speranza
authors.affiliation: Department of Medicine and Science of Aging, University "G. D'Annunzio", Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Patruno
authors.affiliation: Department of Medicine and Science of Aging, University "G. D'Annunzio", Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Felaco
authors.affiliation: Department of Psychological, Humanistic and Territorial Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Grilli
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002097:C-Reactive Protein; D051550:I-kappa B Kinase; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
keywords: Cytokines; Methylation; PANSS; PBMCs; SHP-1; Schizophrenia