Induction of neuronal and myelin-related gene expression by IL-6-receptor/IL-6: a study on embryonic dorsal root ganglia cells and isolated Schwann cells.
The conditional knockdown of the Interleukin-6 (IL-6) family signal transducer (gp130) causes peripheral nerve demyelination and degeneration. In the present work, we investigated the effect of gp130 signaling on peripheral nerves and Schwann cells (SC). We stimulated gp130 signaling with IL6RIL6, a fusion molecule of IL-6 and IL-6R, in rat embryonic day 14 dorsal root ganglia (DRG) cell cultures. In neurons, IL6RIL6 strongly increased the axonal network. In SC, IL6RIL6 favored the appearance of elongated more mature cells versus stellar shaped cells. Gene expression profiling showed an increased expression of neuronal and glial-specific genes. mRNAs related to SC function, including myelin-specific genes, were increased by IL6RIL6 treatment of DRG cells, or of purified SCs isolated from rat sciatic nerve. In IL6RIL6-treated cells, immunostaining showed a strong nuclear signal for Krox-20, a transcription factor essential for differentiation of the SC lineage. On the contrary, we observed that IL6RIL6 inhibited the genes related to TGF-beta family as well as the production of smooth muscle actin.
Zhang
Pei-Lin
PL
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Levy
Alon M
AM
Ben-Simchon
Levana
L
Haggiag
Shalom
S
Chebath
Judith
J
Revel
Michel
M
D000818:Animals; D001369:Axons / Q000187:drug effects; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005727:Ganglia, Spinal / Q000196:embryology*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015850:Interleukin-6 / Q000494:pharmacology*; D009186:Myelin Sheath / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000196:embryology*
D051767:Early Growth Response Protein 2; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; C104543:interleukin 6-interleukin 6 receptor fusion protein, recombinant; D050822:Cytokine Receptor gp130