Lipopolysaccharide-promoted proliferation of endometriotic stromal cells via induction of tumor necrosis factor alpha and interleukin-8 expression

Fertil Steril. 2004 Oct;82 Suppl 3:1036-42. doi: 10.1016/j.fertnstert.2004.04.038.

Abstract

Objective: To evaluate the effect of lipopolysaccharide (LPS) on the expression of tumor necrosis factor alpha (TNFalpha) and interleukin-8 (IL-8) protein in endometriotic stromal cells (ESC) and their effect on the proliferation of ESC.

Design: Prospective study.

Setting: Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan.

Patient(s): Seventeen patients who underwent laparoscopic surgery.

Intervention(s): Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary.

Main outcome measure(s): We determined the effect of LPS on the production of TNFalpha and IL-8 and the effect of IL-8 antisense oligonucleotide and nuclear factor-kappaB (NF-kappaB) inhibitor on IL-8 production using ELISA. TNFalpha production was examined by immunocytochemical staining. We determined the effect of LPS and the effect of IL-8 antisense oligonucleotide and NF-kappaB inhibitor on LPS-promoted ESC proliferation.

Result(s): LPS-stimulated ESC produced significant amounts of TNFalpha and IL-8 in a dose- and time-dependent fashion. Adding LPS promoted ESC proliferation. Anti-TNFalpha antibody and anti-IL-8 antibody inhibited the stimulatory effects of LPS. IL-8 antisense oligonucleotide and NF-kappaB inhibitor significantly decreased LPS-induced IL-8 protein production and LPS-induced ESC proliferation.

Conclusion(s): Pelvic inflammation may promote the progression of endometriosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Endometriosis / metabolism
  • Endometriosis / pathology*
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry / methods
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • NF-kappa B / antagonists & inhibitors
  • Oligonucleotides, Antisense / pharmacology
  • Prospective Studies
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Staining and Labeling
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Toll-Like Receptors
  • Tosylphenylalanyl Chloromethyl Ketone / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Interleukin-8
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • NF-kappa B
  • Oligonucleotides, Antisense
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Tosylphenylalanyl Chloromethyl Ketone