title: Interleukin-1beta mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway.
abstract: Neural precursor cells (NPCs) have been experimentally used to repair the damaged nervous system either by exogenous transplantation or by endogenous activation. In post-injury inflammation, an array of cytokines including interleukin-1beta (IL-1beta) are released by host as well as invading immune cells and increased markedly. In the present study, we investigated the effects of IL-1beta on the survival, proliferation, differentiation and migration of NPCs as well as underlying intracellular signaling pathways. NPCs derived from the E16 rat brain were expanded in neurospheres that were found to express IL-1beta, IL-1RI and IL-1RII, but not IL-1alpha and IL-1ra. IL-1beta inhibited the proliferation of NPCs in a dose-dependent manner, an effect that can be reversed by IL-1ra, an antagonist for IL-1 receptor. This inhibitory effect of IL-1beta on NPCs proliferation resulted in part from its effect on increased apoptosis of NPCs. Moreover, IL-1ra did not affect NPCs lineage fate but rather inhibited GFAP expression in differentiated astrocytes. We also found that IL-1ra had no effect on the transmigration of NPCs in vitro. Finally, we showed that the effect of IL-1beta on NPCs proliferation and differentiation appeared to be mediated by SAPK/JNK, but not ERK, P38MAPK nor NF-kappaB pathways. These findings collectively suggest that the inflammatory environment following CNS injuries may influence the ability of NPCs to repair the damage.
authors.affiliation: Department of Neurobiology, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, PR China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Saili
authors.initials: S
authors.lastname: Fu
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wang
authors.forename: Panpan
authors.initials: P
authors.lastname: Yu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hu
authors.forename: Wenli
authors.initials: W
authors.lastname: Gu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xu
authors.forename: Peihua
authors.initials: P
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D048055:Mitogen-Activated Protein Kinase 8 / Q000187:drug effects / Q000378:metabolism*; D009416:Nerve Regeneration / Q000276:immunology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*