Cytokine-induced nuclear factor kappa B activation promotes the survival of developing neurons

Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), cardi otrophin-1 (CT-1), and interleukin 6 (IL-6) comprise a group of structurall y related cytokines that promote the survival of subsets of neurons in the developing peripheral nervous system, but the signaling pathways activated by these cytokines that prevent neuronal apoptosis are unclear. Here, we sh ow that these cytokines activate NF-kappa B in cytokine-dependent developin g sensory neurons. Preventing NF-kappa B activation with a super-repressor I kappa B-alpha protein markedly reduces the number of neurons that survive in the presence of cytokines, but has no effect on the survival response o f the same neurons to brain-derived neurotrophic factors (BDNF), an unrelat ed neurotrophic factor that binds to a different class of receptors. Cytoki ne-dependent sensory neurons cultured from embryos that lack p65, a transcr iptionally active subunit of NF-kappa B, have a markedly impaired ability t o survive in response to cytokines, but respond normally to BDNF There is i ncreased apoptosis of cytokine-dependent neurons in p65(-/-) embryos in viv o, resulting in a reduction in the total number of these neurons compared w ith their numbers in wild-type embryos. These results demonstrate that NF-k appa B plays a key role in mediating the survival response of developing ne urons to cytokines.