Session Title: Inflammation
Presentation Date: Friday, March 14 – Saturday, March 15, 2009
LPS-INDUCED NO PRODUCTION IN MURINE BV-2 CELLS IS DEPENDENT ON THE JNK PATHWAY
C. Pettersson1, K. Reis1, S. Zetterström Fernaeus2, T. Land2
1Stockholm University, Neurochemistry, Stockholm, Sweden, 2Tallinn University, Tallinn, Estonia
Uncontrolled inflammatory reaction is a driving force of the chronic progression of neurodegenerative diseases. Experimental evidence show that suppression of inflammatory processes mitigates neuronal impairment in both in vitro and in vivo models of various neurodegenerative disorders.
Pro-inflammatory molecules induce microglial activation and the release of potentially detrimental factors capable of generating oxidative damage, such as nitric oxide (NO) and reactive oxygen species (ROS).
The inflammogen lipopolysaccharide (LPS) is used to mimic inflammation both in vitro and in vivio. LPS triggers a variety of intracellular signalling cascades leading to the induction of pro-inflammatory proteins e.g inducible nitric oxide synthase (iNOS).
The aim of the present work was to study the effects of the free radical scavenger N-acetyl-L-cysteine (NAC) on the LPS-induced NO production in a murine microglia cell line. Inhibition of ROS by NAC, in LPS-stimulated BV-2 microglial cells, significantly attenuates the NO production as compared to LPS treatment alone. Inhibition of MAPK activities, that are important signalling molecules in inflammation, showed that the JNK inhibitor SP600125 totally abolishes the LPS-induced NO production.
In conclusion, our results indicate that redox-sensitive regulatory mechanism(s) involving MAPK pathways contribute to the induction of NO production in NAC-and LPS-treated BV-2 cells. The involvement of MAPK pathways in redox-sensitive mechanisms responsible for LPS-induced NO production and iNOS expression will be discussed.