Conditioned medium from activated splenocytes increases substance P in sympathetic ganglia

Abstract

Following removal of the presynaptic input to the superior cervical ganglion (SCG) of the neonatal rat, there is an increase in substance P (Kessler et al.: Science 214:335-336, 1981; Kessler and Black: Brain Res 234:182-187, 1982) and the mRNA coding for its prohormone precursor (Roach et al.: Proc Natl Acad Sci USA 84:5078-5081, 1987). However, the functional significance of this increase has been unclear. We report here that SP increases dramatically in cultures of SCG grown in the presence of conditioned medium from con-A-stimulated splenocytes. The effect is mimicked by growing SCG explants in the presence of human recombinant interleukin-1 (hrIL-1) but not hrIL-2. Nerve growth factor (NGF) is not involved in mediating this effect since antibodies to NGF included in the culture fail to alter the lymphokine-induced increase in SP. Moreover, the effect is somewhat specific for SP since the activities of tyrosine hydroxylase, tryptophan hydroxylase, and choline acetyltransferase (enzymes in the biosynthetic pathways for norepinephrine, serotonin, and acetylcholine) are not similarly elevated. Dorsal root ganglia respond with only modest increases in SP. The action of lymphokines in stimulating SP may, therefore, be a ganglion-specific action in promoting recovery following injury.

Cytokine regulation of substance P expression in sympathetic neurons.

“…Treatment of ganglion explant cultures with IL-1f3 significantly increased SP. This observation is consistent with reports (18,19) that treatment of SCG explants with splenocyte conditioned medium (due to its content of IL-1j3) and IL-1f3 stimulated SP levels (18,19). However, explants of the SCG contain many cell types, including fibroblasts, Schwann cells, and macrophages as well as neurons, and the cellular target of IL-1j3 cannot be determined in such explants.…”

Regulation of vasoactive intestinal peptide expression in sympathetic neurons in culture and after axotomy: The role of cholinergic differentiation factor/leukemia inhibitory factor

“…We found that CDF/LIF mRNA assayed by semiquantitative RT-PCR increases after explanation (see also Shadiack et al, 1993) and after axotomy in situ, raising the question ofwhether the signal( s) immediately responsible for inducing CDF/ LIF in nonneuronal cells after neuronal injury are generated within the ganglion. Examination of the regulation of SP expression in culture suggests that IL-1 P is involved (Jonakait et al, 1990;Freidin and Kessler, 1991;Hart et al, 1991;Freidin et al, 1992;Shadiack et al, 1993). Cultured sympathetic neurons synthesize and release IL-10 (Freidin et al, 1992).…”

Substance P gene expression is regulated by interleukin‐1 in cultured sympathetic ganglia

“…Ganglia were harvested after 4-5 days and assayed by RIA for SP-like immunoreactivity (Kessler and Black, 1982;Jonakait and Schotland, 1990) …”

“…Ganglia were harvested after 4-5 days and assayed by RIA for SP-like immunoreactivity (Kessler and Black, 1982;Jonakait and Schotland, 1990) using a polyclonal SP antibody obtained from the laboratory of Ira B . Black (Robert Wood Johnson School of Medicine, UMDNJ).…”