The interleukin-1-induced increase of substance P in sympathetic ganglia is not mediated by ciliary neurotrophic factor.
Interleukin-1 (IL-1) induction of substance P (SP) in cultured sympathetic ganglia requires a soluble intermediate molecule that is present in IL-1 conditioned medium (IL-1CM). One of the required intermediates is leukemia inhibitory factor (LIF; Shadiack et al., J Neurosci 13:2601-2609, 1993). In the present study we have examined the possibility that ciliary neurotrophic factor (CNTF) is another intermediate involved in the IL-1 induction of sympathetic SP. CNTF mimics the action of IL-1CM by raising both SP and choline acetyltransferase activity--actions that are blocked by a specific neutralizing antiserum for CNTF. However, IL-1CM and CNTF differ in their response to depolarizing agents: while KCl (40 mM) blocks the action of IL-1CM (and LIF), it enhances the action of CNTF. Furthermore, neither CNTF bioactivity nor CNTF protein is detected in IL-1CM. Neutralizing antiserum to CNTF fails to block the action of either IL-1 or IL-1CM, suggesting that neither a soluble nor a membrane-bound form of the molecule is active in direct response to IL-1 action. While Northern blots confirm the presence of both CNTF and CNTF receptor mRNA in neonatal ganglia, neither culturing nor IL-1 treatment alters these mRNA levels. These data taken together suggest that while CNTF is present and possibly active in sympathetic ganglia, it is not a mediator of the IL-1 induction of SP.
Ding
M
M
Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102.
Hart
R P
RP
Shadiack
A M
AM
Jonakait
G M
GM
D000818:Animals; D000831:Animals, Newborn; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D046508:Culture Techniques; D004594:Electrophysiology; D004790:Enzyme Induction; D005728:Ganglia, Sympathetic / Q000378:metabolism* / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D013373:Substance P / Q000378:metabolism*
D020934:Ciliary Neurotrophic Factor; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D013373:Substance P; D002795:Choline O-Acetyltransferase