title: PGE1 Attenuates IL-1β-induced NGF Expression in Human Intervertebral Disc Cells.
abstract: METHODS
  In vitro study using isolated human intervertebral disc (IVD) cells.
  
  
  OBJECTIVE
  To investigate the effects of prostaglandin (PG)E1 and its orally available derivative limaprost on the regulation of nerve growth factor (NGF) expression and to compare their actions with other prostanoids using interleukin (IL)-1-stimulated human IVD cells.
  
  
  BACKGROUND
  We previously reported that a selective COX-2 inhibitor enhanced, whereas PGE2 suppressed the induction of NGF by IL-1 in human IVD cells, and proposed that PGE2 can suppress NGF expression by a negative feedback mechanism.
  
  
  METHODS
  Isolated human IVD cells were stimulated with IL-1 in the presence or absence of increasing concentrations of PGE2, PGE1, limaprost, PGI2, PGD2, or PGF2α (10-10,000 nM). For some experiments, an E-series prostanoid receptor (EP)4 antagonist (L-161,982) was added prior to the stimulation. NGF expression was determined by real-time polymerase chain reaction and its protein level was quantified by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  PGE2, PGE1, and limaprost inhibited the IL-1-mediated induction of NGF in a concentration-dependent manner, with IC50 values of 9.9, 10.6, and 70.9 nM, respectively. PGI2 also suppressed NGF expression but to a much less extent. PGD2, on the other hand, significantly enhanced NGF expression, whereas PGF2α had no effect. Protein expression levels of NGF mirrored its mRNA levels. The suppression of NGF expression by PGE2 and PGE1 was partly reversed by L-161,982.
  
  
  CONCLUSIONS
  PGE1 and limaprost exhibited a novel pharmacological action that suppresses NGF expression in human IVD cells, and other prostanoids differentially regulated NGF expression. Limaprost has been used to treat patients with lumbar spinal stenosis in Japan and was proved to be effective in relieving symptoms. Our in vitro results may explain, in part, the mechanism of action of limaprost for low back pain.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Orthopedic Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Murata
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Sawaji
authors.forename: Wuqikun
authors.initials: W
authors.lastname: Alimasi
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Kenji
authors.initials: K
authors.lastname: Endo
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Makiko
authors.initials: M
authors.lastname: Yorifuji
authors.forename: Taiichi
authors.initials: T
authors.lastname: Kosaka
authors.forename: Takaaki
authors.initials: T
authors.lastname: Shishido
authors.forename: Kengo
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000527:Alprostadil / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; C502240:NGF protein, human; D020932:Nerve Growth Factor; D000527:Alprostadil