Interleukin-6 is required for the early induction of glial fibrillary acidic protein in Schwann cells during Wallerian degeneration.
Signal transducer and activator of transcription 3 (STAT3) regulates gene transcription in response to cytokines and growth factors. In the central nervous system, STAT3 plays a role in neuroprotection and reactive gliosis after lesions. During peripheral nerve regeneration, a nerve injury-induced up-regulation of cytokines and growth factors accompanies STAT3 activation in sensory neurons and Schwann cells (SCs) even though its molecular details and functions are unknown. We then analyzed the ligands and functions of STAT3 activation in RT4 schwannoma cells and adult SCs in vitro and in vivo. We have identified that interleukin-6 (IL-6), but not ciliary neurotrophic factor, leukemia inhibitory factor, or ligands for receptor tyrosine kinases, activates STAT3 in SCs. The IL-6/STAT3 signaling in primary SCs and RT4 cells induced the gene expression of glial fibrillary acidic protein (GFAP), which is known to be required for the proper regeneration of the injured nerves. Finally, the GFAP induction in the sciatic nerves after injury was significantly delayed in IL-6-deficient mice. These findings indicate that IL-6 plays an important role in STAT3-dependent GFAP induction in SCs during peripheral nerve regeneration.
Lee
Hyun Kyoung
HK
Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University, Busan, South Korea.
Seo
In Ae
IA
Suh
Duk Joon
DJ
Hong
Jeong-In
JI
Yoo
Young Hyun
YH
Park
Hwan Tae
HT
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D050822:Cytokine Receptor gp130 / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism; D014855:Wallerian Degeneration / Q000378:metabolism*
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D050822:Cytokine Receptor gp130; D008156:Luciferases