title: Induction of the neurokinin 1 receptor by TNFα in endometriotic tissue provides the potential for neurogenic control over endometriotic lesion growth.
abstract: BACKGROUND
  Endometriosis is characterized by the growth of ectopic endometrial tissue. Nerve fibers are frequently associated with ectopic lesions, and neurogenic inflammation may play a role in endometriosis.
  
  
  OBJECTIVE
  The purpose of this study was to determine the presence of tachykinin receptors in endometriotic lesions and the role of TNFα on their expression.
  
  
  METHODS
  This study was an assessment of matching eutopic and ectopic endometrial tissue and peritoneal fluid from patients with endometriosis and an in vitro analysis of primary endometrial cells.
  
  
  METHODS
  The setting was a university hospital.
  
  
  METHODS
  Participants were premenopausal women undergoing laparoscopy.
  
  
  METHODS
  Endometriotic lesions were removed surgically.
  
  
  METHODS
  Tachykinin mRNA (TACR1/2) and protein (neurokinin 1 receptor [NK1R]) expression in both eutopic and ectopic endometrial tissue from patients with endometriosis and the correlation to peritoneal fluid TNFα were measured. Primary endometrial epithelial and stromal cells were assessed in vitro to determine the induction of TACR1/2 and NK1R expression after TNFα treatment. Cell viability of endometrial stromal cells after substance P exposure was also assessed.
  
  
  RESULTS
  Expression of both TACR1 and TACR2 mRNA was significantly higher in the ectopic than in the eutopic tissue. Both TACR1 mRNA and NK1R protein expression was significantly correlated with peritoneal fluid TNFα, and in vitro studies confirmed that TNFα treatment induced both TACR1 mRNA and NK1R protein expression in endometrial stromal cells. In endometrial stromal cells, substance P treatment enhanced cell viability, which was inhibited by a specific NK1R antagonist.
  
  
  CONCLUSIONS
  NK1R expression is induced in ectopic endometrial tissue by peritoneal TNFα. Induction of NK1R expression may permit endometriotic lesion maintenance via exposure to substance P.
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, University of Berne, Berne, CH-3010, Switzerland. brett.mckinnon@dkf.unibe.ch
authors.forename: Brett D
authors.initials: BD
authors.lastname: McKinnon
authors.forename: Jakob
authors.initials: J
authors.lastname: Evers
authors.forename: Nick A
authors.initials: NA
authors.lastname: Bersinger
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mueller
mesh_terms: D004715:Endometriosis / Q000209:etiology* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger / Q000032:analysis; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000235:genetics; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018039:Receptors, Tachykinin; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P