title: Pyrrolidine dithiocarbamate attenuates nuclear factor-ĸB activation, cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic epithelial cells.
abstract: BACKGROUND
  The nuclear factor-κB (NF-κB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis.
  
  
  METHODS
  The phosphorylation of IκB, expression of nuclear p65 protein and NF-κB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E(2) (PGE(2)) production of EECs was measured by ELISA.
  
  
  RESULTS
  PDTC in the absence or presence of tumor necrosing factor-α (TNF-α) showed stronger inhibitory effects on IκB phosphorylation, expression of nuclear p65 protein and NF-κB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE(2) synthesis.
  
  
  CONCLUSIONS
  PDTC may represent a novel therapeutic strategy for treatment of endometriosis.
authors.affiliation: Departments of Obstetrics and Gynecology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Zhi-ming
authors.initials: ZM
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Zhang
authors.forename: Hong-ying
authors.initials: HY
authors.lastname: Dai
authors.forename: Xin-qiang
authors.initials: XQ
authors.lastname: Ji
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Xu-fu
authors.initials: XF
authors.lastname: Wang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D015345:Oligonucleotide Probes; D010766:Phosphorylation; D011759:Pyrrolidines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017931:DNA Primers; D020672:I-kappa B Proteins; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011759:Pyrrolidines; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D051546:Cyclooxygenase 2; D015232:Dinoprostone