Nitric oxide production: a mechanism of Chlamydia trachomatis inhibition in interferon-gamma-treated RAW264.7 cells

FEMS Immunol Med Microbiol. 1996 Jun;14(2-3):109-20. doi: 10.1111/j.1574-695X.1996.tb00277.x.

Abstract

IFN-gamma and/or LPS induced nitrite production and inhibition of Chlamydia trachomatis (CT) replication in the murine macrophage cell line, RAW264.7. Linear regression analysis demonstrated a strong correlation between nitrite production and inhibition of CT replication (correlation coefficients: -0.93, P < 0.001). L-NMMA specifically inhibited nitrite production and restored CT replication (55-71%). Inducible nitric oxide synthase (iNOS) mRNA was analyzed by Northern and dot blot hybridization with an iNOS cDNA probe. A strong correlation between iNOS mRNA expression and inhibition of CT replication also was observed (correlation coefficient: -0.97, P < 0.05). Furthermore, anti-TNF-alpha antibody, which completely neutralized biological activity of the secreted TNF-alpha, neither inhibited nitrite production nor restored CT replication in the LPS- and/or IFN-gamma-treated RAW264.7 cells. In mouse peritoneal macrophages treated with IFN-gamma, both L-NMMA and anti-TNF-alpha antibody inhibited nitrite production and restored CT replication. However, L-NMMA and the antibody had no effect upon nitrite production and CT inhibition in LPS-treated peritoneal macrophages. These data indicate that NO production is one mechanism for inhibition of CT replication in IFN-gamma-activated murine macrophages.

MeSH terms

  • Animals
  • Cell Line
  • Chlamydia trachomatis / growth & development*
  • Dose-Response Relationship, Drug
  • Interferon-gamma / pharmacology*
  • Linear Models
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / microbiology*
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Nitrites / metabolism
  • RNA, Bacterial / analysis
  • RNA, Messenger / analysis
  • Tryptophan / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • omega-N-Methylarginine / pharmacology

Substances

  • Lipopolysaccharides
  • Nitrites
  • RNA, Bacterial
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • omega-N-Methylarginine
  • Nitric Oxide
  • Interferon-gamma
  • Tryptophan
  • Nitric Oxide Synthase