Interleukin-1 involvement in the induction of leukemia inhibitory factor mRNA expression following axotomy of sympathetic ganglia
Interleukin-1 involvement in the induction of leukemia inhibitory factor mRNA expression following axotomy of sympathetic ganglia
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DOI：
10.1016/s0165-5728(96)00115-4
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发表时间：
1996-11-01
影响因子：
3.3
通讯作者：
Hart, RP
中科院分区：
文献类型：
--
作者：
Carlson, CD;Bai, YC;Hart, RP
颈上交感神经节（SCG）轴切术导致神经肽基因表达增加。在体外，暴露于炎症细胞因子白介素- 1 （IL-I）下，神经肽基因表达也同样增加。IL-1在体外的作用是由白血病抑制因子（leukemia inhibitory factor， LIF）介导的。由于IL-1通过体外LIF调节神经肽的表达，我们想知道体内的axotomy是否会导致LIF mRNA的增加，以及这种增加是否受到IL-1活性的调节。在切开后6小时内，神经节LIF mRNA显著升高。此外，肛门切开术可使节内IL-1 β mRNA快速短暂增加，随后ICAM-1 mRNA迅速增加，从而提示IL-1活性的局部来源。抗炎药地塞米松（DEX）预处理可降低腋切开术后IL-1 β和LIF mrna的升高。编码特定信号转导I型IL-1受体的mRNA在体内未受损的SCG中存在，并且在轴切后增加。体内局部应用IL-1 β，即使在未损伤的神经节中也能诱导LIF mRNA，但其程度不及腋切开术。DEX治疗阻断了IL-1 β介导的LIF mRNA的增加。因此，DEX通过抑制il - 1的产生及其对LIF基因表达的作用来阻断LIF mRNA的诱导。纯合子il - 1受体I型基因敲除小鼠的轴切开术导致SCG中LIF mRNA的诱导延迟和/或减少，但不阻止LIF mRNA的表达。我们得出的结论是，虽然IL-1可能参与了轴切开术后的基因表达级联，但它本身不足以介导轴切开术对LIF mRNA的完全诱导。
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-l (IL-I). 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-I 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-I and its action on LIF gene expression. Axotomy of a homozygous IL-I 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.