Leukemia inhibitory factor induces neurotrophic effects and TrkA/PI3K/Akt activation in dorsal root ganglion neurons = Leukemia inhibitory factor induces neurotrophic effects and TrkA/PI3K/Akt activation in dorsal root ganglion neurons

다국어 초록 (Multilingual Abstract)

Background: Myokines could be associated with peripheral inflammation. The impaired skin barrier function triggers abnormal muscle contraction leading to an increased neurosensory response and neurogenic inflammation.
Objectives: The aim of this study was to verify that the specific myokine, leukemia inhibitory factor (LIF), could have meaningful roles on aggravation of pruritus in chronic inflammatory skin disorders.
Methods: An in vitro coculture model between dorsal root ganglion (DRG) neurons and keratinocytes was adopted for assessment of possible trophic effect. The activation of serial signaling pathways in DRG neurons by LIF and/or nerve growth factor (NGF) were examined.
Results: LIF treatment to DRG neurons showed significant neurite outgrowth comparable with NGF. LIF also meaningfully affected axonal growth in coculture models. The LIF induced neurotrophic effects were effectively diminished by TrkA inhibitor, K252a. LIF application resulted in time- and dose-dependent tropomyosin receptor kinase A (TrkA) and Akt phosphorylation in DRG neurons. In addition, TrkA and Akt phosphorylation by LIF in DRG neurons were effectively prohibited with TrkA inhibitor, K252a respectively. Lastly, Akt phosphorylation induced by LIF was also meaningfully restrained by phosphoinositide 3-kinase (PI3K) inhibitor, LY-294002.
Conclusion: LIF could cause increased neurite outgrowth and activation of TrkA/PI3K/Akt phosphorylation in DRG neurons.