title: Interleukin-8 overexpression in astrocytomas is induced by prostaglandin E2 and is associated with the transcription factors CCAAT/enhancer-binding protein-β and CCAAT/enhancer-binding homologous protein.
abstract: BACKGROUND
  The upregulation of microsomal prostaglandin E synthase-1 (mPGES-1) and the overexpression of interleukin-8 (IL-8) have been separately linked to glioma malignancy.
  
  
  OBJECTIVE
  To evaluate (1) the correlation between the mRNA levels of IL-8, mPGES-1, and the main transcription factors (TFs) activating the IL-8 promoter in human brain tumors of different grades; (2) the role of prostaglandin E2 (PGE2) on IL-8 activation and the expression of these TFs in tumor-derived cells; and (3) the biological impact of PGE2 treatment and mPGES-1 silencing on IL-8 synthesis and tumorigenesis.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction, transfection experiments, and cell proliferation and apoptosis assays were performed.
  
  
  RESULTS
  Regardless of histological grade, a significant positive association between IL-8 expression and mPGES-1, CCAAT/enhancer-binding protein-β (C/EBP-β) and C/EBP Homologous Protein (CHOP) mRNA levels was found only in astrogliomas (P < .001). The correlation was not significant in the other brain tumors. PGE2-treated astroglioma cells showed a marked upregulation of IL-8, C/EBP-β, and CHOP, as well as increased proliferation and decreased apoptosis compared with untreated cells. mPGES-1-silenced astroglioma cells displayed decreased IL-8 synthesis, accompanied by reduced cell growth and an increased rate of apoptosis. The other brain tumor cells were unaffected either by PGE2 treatment or by mPGES-1 knockout.
  
  
  CONCLUSIONS
  (1) PGE2 is responsible for IL-8 overexpression, independently of the malignancy grade, in astrogliomas only. (2) C/EBP-β and CHOP may be involved in mediating PGE2-induced IL-8 activation in these tumors. (3) mPGES-1 inhibition may have potential as a form of adjuvant therapy for astrogliomas.
authors.affiliation: Department of Neurosciences, Psychiatry and Anaesthesiology, Neurosurgical Clinic, University of Messina, Messina, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Venza
authors.forename: Maria
authors.initials: M
authors.lastname: Visalli
authors.forename: Concetta
authors.initials: C
authors.lastname: Alafaci
authors.forename: Maria
authors.initials: M
authors.lastname: Caffo
authors.forename: Gerardo
authors.initials: G
authors.lastname: Caruso
authors.forename: Francesco Maria
authors.initials: FM
authors.lastname: Salpietro
authors.forename: Francesco
authors.initials: F
authors.lastname: Tomasello
authors.forename: Diana
authors.initials: D
authors.lastname: Teti
mesh_terms: D017209:Apoptosis; D001254:Astrocytoma / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015232:Dinoprostone / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005910:Glioma / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D016209:Interleukin-8; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051742:Transcription Factor CHOP; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone