Cytokines and neurotrophic factors fail to affect Nogo-A mRNA expression in differentiated human neurones: implications for inflammation-related axonal regeneration in the central nervous system.
Nogo is a novel myelin-associated inhibitor of neurite outgrowth which regulates stable neuronal connections during axonal regeneration following injury in the adult mammalian central nervous system (CNS). Because cytokines and neurotrophic factors play a key role in inflammation-related axonal regeneration, we investigated: (i) the constitutive expression of Nogo and the Nogo receptor (NgR) mRNA in human neural cell lines; (ii) Nogo and NgR mRNA levels in the NTera2 human teratocarcinoma cell line during retinoic acid (RA)-induced neuronal differentiation; and (iii) their regulation in NTera2-derived differentiated neurones (NTera2-N) after exposure to a battery of cytokines and growth factors potentially produced by activated glial cells at post-traumatic inflammatory lesions in the CNS. By reverse transcriptase-polymerase chain reaction analysis, the constitutive expression of Nogo-A, the longest isoform of three distinct Nogo transcripts and NgR mRNA was identified in a wide variety of human neural and non-neural cell lines. By Northern blot analysis, the levels of Nogo-A mRNA were elevated markedly in NTera2 cells following RA-induced neuronal differentiation, accompanied by an increased expression of the neurite growth-associated protein GAP-43 mRNA. In contrast, Nogo-A, Nogo-B, NgR and GAP-43 mRNA levels were unaltered in NTera2-N cells by exposure to basic fibroblast growth factor, brain-derived neurotrophic factor, glia-derived neurotrophic factor, tumour necrosis factor-alpha, interleukin-1beta, dibutyryl cyclic AMP or phorbol 12-myristate 13-acetate. These results indicate that both Nogo-A and NgR mRNA are coexpressed in various human cell types, including differentiated neurones, where their expression is unaffected by exposure to a panel of cytokines and neurotrophic factors which might be involved in inflammation-related axonal regeneration in the CNS.
Satoh
J-I
JI
Division of Neurology, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. satoj1@post.saga-med.ac.jp
Kuroda
Y
Y
D001369:Axons / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002493:Central Nervous System Diseases / Q000503:physiopathology; D016207:Cytokines / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000235:genetics; D058851:GPI-Linked Proteins; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009185:Myelin Proteins / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D019922:GAP-43 Protein; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D009414:Nerve Growth Factors; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D012333:RNA, Messenger; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface