Interleukin-1 involvement in the induction of leukemia inhibitory factor mRNA expression following axotomy of sympathetic ganglia.
Axotomy of superior cervical (sympathetic) ganglia (SCG) results in increased neuropeptide gene expression. In vitro, neuropeptide gene expression is similarly increased by exposure to the inflammatory cytokine interleukin-1 (IL-1). The effect of IL-1 in-vitro has been shown to be mediated by leukemia inhibitory factor (LIF). Since IL-1 regulates neuropeptide expression via LIF in vitro, we asked whether axotomy in vivo produces an increase in LIF mRNA, and whether that increase is regulated by IL-1 activity. Within 6 h following axotomy, ganglionic LIF mRNA is substantially elevated. Moreover, axotomy produces a rapid and transient increase in intraganglionic IL-1 beta mRNA, followed rapidly by an increase in ICAM-1 mRNA, thereby suggesting a local source of IL-1 activity. Pretreatment with the anti-inflammatory agent dexamethasone (DEX) reduces the increases of both IL-1 beta and LIF mRNAs following axotomy. mRNA encoding the specific signal-transducing Type I IL-1 receptor is present in unlesioned SCG in vivo, and increases following axotomy. Local application of IL-1 beta in vivo induces LIF mRNA even in uninjured ganglia, though not to the extent seen with axotomy. DEX treatment blocks this IL-1 beta-mediated increase in LIF mRNA. Therefore, DEX blocks the induction of LIF mRNA by inhibiting both the production of IL-1 and its action on LIF gene expression. Axotomy of a homozygous IL-1 receptor type I gene knockout mouse leads to a delayed and/or diminished induction of LIF mRNA in SCG, but does not prevent LIF mRNA expression. We conclude that while IL-1 is likely to be involved in the cascade of gene expression that follows axotomy, it alone is not sufficient to mediate the full induction of LIF mRNA by axotomy.
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
C D
CD
Carlson
Y
Y
Bai
M
M
Ding
G M
GM
Jonakait
R P
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Hart
D000818:Animals; D001483:Base Sequence; D003714:Denervation; D003907:Dexamethasone / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000235:genetics*; D007249:Inflammation / Q000503:physiopathology; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; D003907:Dexamethasone