Tumor necrosis factor-alpha induces substance P in sympathetic ganglia through sequential induction of interleukin-1 and leukemia inhibitory factor

Journal of Neurobiology
M DingG M Jonakait

Abstract

The present study establishes that tumor necrosis factor-alpha (TNF-alpha) induction of sympathetic substance P (SP) requires sequential induction of both interleukin (IL-1) and leukemia inhibitory factor (LIF). TNF-alpha dose-dependently induces SP, an induction that is secondary to an increase in the SP precursor, preprotachykinin (PPT), mRNA. Since TNF-alpha conditioned medium (CM) mimics the effect of TNF-alpha by raising SP, actions that are not antagonized by a neutralizing TNF-alpha antibody, TNF-alpha induction of SP is mediated by a soluble intermediate or intermediates. The blockade of TNF-alpha action by a specific IL-1 receptor antagonist and the induction of IL-1 mRNA by TNF-alpha suggest that IL-1 is one of the intermediates. Moreover, because immunoprecipitation with LIF antibodies decreases SP-inducing activity of TNF-alpha CM, and because LIF mRNA is also induced by TNF-alpha, LIF is a second intermediate. Furthermore, TNF-alpha-induced LIF mRNA is blocked by the IL-1 receptor antagonist, whereas IL-1-induced LIF mRNA is not affected by TNF-alpha antibodies, suggesting that TNF-alpha first induces IL-1, and IL-1 subsequently induces LIF. These data suggest that TNF-alpha induces SP in sympathetic ganglia throug...Continue Reading

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Citations

Mar 18, 2009·Experimental Brain Research·Nurcan UçeylerClaudia Sommer
Jun 8, 2006·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Masayuki MiyagiKazuhisa Takahashi
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