IL-1beta promotes neurite outgrowth by deactivating RhoA via p38 MAPK pathway.
Expression of the pro-inflammatory cytokine interleukin-1 beta (IL-1beta) is increased following the nervous system injury. Generally IL-1beta induces inflammation, leading to neural degeneration, while several neuropoietic effects have also been reported. Although neurite outgrowth is an important step in nerve regeneration, whether IL-1beta takes advantages on it is unclear. Now we examine how it affects neurite outgrowth. Following sciatic nerve injury, expression of IL-1beta is increased in Schwann cells around the site of injury, peaking 1 day after injury. In dorsal root ganglion (DRG) neurons and cerebellar granule neurons (CGNs), neurite outgrowth is inhibited by the addition of myelin-associated glycoprotein (MAG), activating RhoA. IL-1beta overcomes MAG-induced neurite outgrowth inhibition, by deactivating RhoA. Intracellular signaling experiments reveal that p38 MAPK, and not nuclear factor-kappa B (NF-kappaB), mediated this effect. These findings suggest that IL-1beta may contribute to nerve regeneration by promoting neurite outgrowth following nerve injury.
Temporin
Ko
K
Department of Orthopaedics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Tanaka
Hiroyuki
H
Kuroda
Yusuke
Y
Okada
Kiyoshi
K
Yachi
Koji
K
Moritomo
Hisao
H
Murase
Tsuyoshi
T
Yoshikawa
Hideki
H
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D053583:Interleukin-1beta / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D053583:Interleukin-1beta; D048051:p38 Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein