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. CONCLUSION: (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.

Interleukin-8 (IL-8) overexpression in astrocytomas is induced by prostaglandin E2 (PGE2) and is associated to the transcription factors CCAAT enhancer binding protein-beta (C/EBP-β) and C/EBP Homologous Protein (CHOP)

VENZA, Mario;VISALLI, Maria;ALAFACI, Concetta;CAFFO, Maria;SALPIETRO, Francesco;TOMASELLO, Francesco;TETI, Diana
2011-01-01

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. CONCLUSION: (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.
2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1910660
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