Interleukin-6 upregulates the expression of PMP22 in cultured rat Schwann cells via a JAK2-dependent pathway.
The interleukin-6 (IL-6) family of cytokines is thought to be involved in the development and regeneration of peripheral nerves; however, their roles in myelination remain unclear. In this study, we examined the effects of IL-6 on the expression of genes for compact myelin proteins using Schwann cell cultures prepared by multiple explantation of adult rat sciatic nerves. In semi-quantitative reverse transcription-polymerase chain reaction analysis, stimulation of Schwann cells with IL-6 significantly increased the mRNA level of peripheral myelin protein 22 (PMP22), but not those of myelin protein zero and myelin basic protein. The increase in PMP22 mRNA was markedly suppressed by AG490, a Janus kinase 2 (JAK2) inhibitor, but not significantly by PD098059, a mitogen-activated protein kinase inhibitor. Immunocytochemical staining revealed that IL-6 enhanced immunoreactivities for the phosphorylated forms of both JAK2 and signal transducer and activator of transcription 3 (STAT3), as well as that for PMP22. These results indicate that IL-6 can enhance PMP22 production in Schwann cells via a JAK2-dependent pathway by probably activating STAT3 and thus may contribute to myelination.
Ito
Takaaki
T
Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Ikeda
Kazuo
K
Tomita
Katsuro
K
Yokoyama
Shigeru
S
D000818:Animals; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics; D018993:Myelin P0 Protein / Q000096:biosynthesis / Q000235:genetics; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D015850:Interleukin-6; D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D050822:Cytokine Receptor gp130; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases