Regulation of IL-18 production by IFN gamma and PGE2 in mouse microglial cells: involvement of NF-kB pathway in the regulatory processes

Immunol Lett. 2001 Jun 1;77(2):79-85. doi: 10.1016/s0165-2478(01)00209-7.


Interleukin (IL)-18, a recently identified proinflammatory cytokine, has been implicated in a variety of pathological conditions such as rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory liver injury. Microglial cells are the primary cellular source of IL-18 in the brain. Along with other inflammatory mediators in the central nervous system (CNS), IL-18 may play an important role in the pathogenesis of various neurodegenerative diseases. To understand how lymphokines and lipid mediators participate in the regulation of microglial IL-18 production, we assessed the effects of interferon (IFN)gamma, one of the major macrophage-activating lymphokines, and prostaglandin (PG)E(2), a lipid mediator produced in the brain, on IL-18 production and the expression of the IL-18 processing enzyme, caspase-1, in mouse microglial cells. IFNgamma increased lipopolysaccharide (LPS)-induced IL-18 production and caspase-1 expression, while PGE(2) inhibited LPS-induced IL-18 production. A similar pattern of IL-18 regulation by IFNgamma and PGE(2) was observed at the mRNA level. The regulation of microglial activation by IFNgamma and PGE(2) was accompanied by differential modulation of LPS-induced NF-kB activation. While IFNgamma enhanced LPS-induced NF-kB activation, PGE(2) suppressed its activation. These results indicate that IFNgamma and PGE(2) are the important regulators of proinflammatory microglial activation in CNS, and suggest the involvement of NF-kB pathway in these regulatory processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Caspase 1 / biosynthesis
  • Cell Line
  • Cells, Cultured
  • Dinoprostone / pharmacology*
  • Interferon-gamma / pharmacology*
  • Interleukin-18 / biosynthesis*
  • Interleukin-18 / genetics
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / immunology
  • Microglia / metabolism*
  • NF-kappa B / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Transcription, Genetic / immunology


  • Interleukin-18
  • Lipopolysaccharides
  • NF-kappa B
  • Interferon-gamma
  • Caspase 1
  • Dinoprostone