LIF-AND IL-1 BETA-MEDIATED INCREASES IN SUBSTANCE-P RECEPTOR MESSENGER-RNA IN AXOTOMIZED, EXPLANTED OR DISSOCIATED SYMPATHETIC-GANGLIA

Regulation of substance P receptor (SPR) mRNA was examined in the rat sympathetic superior cervical ganglion (SCG) in vitro and in vivo afte r axotomy. Interleukin-1 beta (IL-1 beta) treatment of explanted gangl ia elevated levels of SPR mRNA. By contrast, dissociated cultures of p urified sympathetic neurons, purified fibroblasts, and purified Schwan n cells each expressed only low levels of SPR mRNA, and treatment with the cytokine did not alter levels of the receptor mRNA. Treatment of Schwann cell or fibroblast cultures with leukemia inhibitory factor (L IF) also did not alter SPR mRNA. However, treatment of pure neuronal c ultures with LIF significantly elevated levels of the receptor mRNA. F urther, SPR mRNA increased in pure sympathetic neurons cultured in the presence of conditioned medium from IL-1 beta treated fibroblasts or Schwann cells; this effect was blocked in the presence of LIF antibody . This suggests that the stimulatory effects of IL-1 beta on SPR mRNA in explants is mediated by LIF release. Axotomy of the SCG in vivo res ulted in a significant increase in LIF mRNA. Further, axotomy resulted in a significant increase in SPR mRNA, suggesting that LIF may mediat e the increase in SPR mRNA. In view of the known effects of substance P (SP) on inflammatory responses, these observations suggest that coor dinated expression of SP and SPR mRNA in neurons after nerve injury ma y participate in inflammatory and repair processes in the ganglion.