Induction of pro inflammatory molecules in mice with amyotrophic lateral sclerosis:: No requirement for proapoptotic interleukin-1β in neurodegeneration

Recent studies have demonstrated the activation of caspase-1 and caspase-3 in mice expressing mutant superoxide dismutase 1 (SOD1), models of amyotrophic lateral sclerosis. Caspase-1 converts the prointerleukin-1 beta into a potent proinflammatory molecule involved in the innate immune response and in neurodegenerative diseases. We report on the chronic expression of interleukin-1 beta mRNA in the spinal cord of SOD1(G37R) mice, together with robust mRNA expression for the nuclear factor-kappaB (NF-kappaB) inhibitor I kappaB alpha, for other proinflammatory cytokines and chemokines (interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1) and for the toll-like receptor TLR2 involved in innate immunity. To further assess the interleukin-1 beta contribution to neurodegeneration, we generated mice expressing SOD1(G37R) to a context of interleukin-1 beta gene knockout. Surprisingly, the absence of interleukin-1 beta had no. effect on the life span of SOD1(G37R) mice, nor on the extent of motor axon degeneration at age 7 and 10 months. Whereas neither compensatory induction of the interleukin-1 alpha, mRNA nor increases in mRNA levels for I kappaB alpha, tumor necrosis factor-alpha and macrophage chemoattractant protein-1 occurred as a result of interleukin-1 beta gene disruption, enhanced levels of TLR2 mRNA were detected in SOD1(G37R) mice lacking interleukin-1 beta. We conclude that interleukin-1 beta does not directly contribute to motor neuron degeneration in SOD1(G37R) mice, but it may act as a modulator of the innate immune response.