Detoxication enzyme inducers modify cytokine production in rat mixed glial cells

J Neuroimmunol. 2005 Sep;166(1-2):132-43. doi: 10.1016/j.jneuroim.2005.05.013.


Pro-inflammatory cytokines, e.g. interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha) as well as neurotoxic molecules such as nitric oxide (NO), that are produced and released by activated glial cells, play an important role in inflammation and oxidative stress occurring during Multiple Sclerosis (MS). Reduction of these processes could therefore be of therapeutic interest. Dimethylfumarate (DMF) and sulforaphane (SP) are well known for their detoxicating properties. Furthermore, they have anti-inflammatory effects as shown clinically by the treatment of inflammatory skin diseases. However, their detoxication and anti-inflammatory action on brain-derived cells is unknown. In the present study we have studied, within the same concentration range, the anti-inflammatory and detoxicating effects of DMF and SP on the production and release of mediators of inflammation and detoxication from lipopolysaccharide (LPS) activated primary co-cultures of rat microglial and astroglial cells. DMF and SP attenuated the LPS-induced production and release of TNFalpha, IL-1beta, IL-6 and NO. In addition, DMF and SP increase both mRNA level and activity of NAD(P)H:quinone reductase (NQO-1), a detoxication enzyme, as well as the cellular glutathione content. We conclude that DMF or SP simultaneously can (1) reduce mediators of inflammation and (2) enhance detoxication enzymes in LPS stimulated co-cultures of astroglial and microglial cells. This double-sided effect could potentially be of therapeutic interest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Dimethyl Fumarate
  • Enzyme Induction / drug effects
  • Fumarates / pharmacology*
  • Glutathione / metabolism
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Isothiocyanates
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Neuroglia / drug effects*
  • Neuroglia / metabolism*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Nitrites / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Thiocyanates / pharmacology*
  • Time Factors
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Fumarates
  • Interleukin-1
  • Interleukin-6
  • Isothiocyanates
  • Nitrites
  • RNA, Messenger
  • Thiocyanates
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • NAD(P)H Dehydrogenase (Quinone)
  • Dimethyl Fumarate
  • sulforaphane
  • Glutathione