title: Leukaemia inhibitory factor stimulates proliferation of olfactory neuronal progenitors via inducible nitric oxide synthase.
abstract: Neurogenesis continues in the adult brain and in the adult olfactory epithelium. The cytokine, leukaemia inhibitory factor and nitric oxide are both known to stimulate neuronal progenitor cell proliferation in the olfactory epithelium after injury. Our aim here was to determine whether these observations are independent, specifically, whether leukaemia inhibitory factor triggers neural precursor proliferation via the inducible nitric oxide synthase pathway. We evaluated the effects of leukaemia inhibitory factor on inducible form of nitric oxide synthase (iNOS) expression, and cell proliferation in olfactory epithelial cell cultures and olfactory neurosphere-derived cells. Leukaemia inhibitory factor induced expression of iNOS and increased cell proliferation. An iNOS inhibitor and an anti-leukaemia inhibitory factor receptor blocking antibody inhibited leukaemia inhibitory factor-induced cell proliferation, an effect that was reversed by a NO donor. Altogether, the results strongly suggest that leukaemia inhibitory factor induces iNOS expression, increasing nitric oxide levels, to stimulate proliferation of olfactory neural precursor cells. This finding sheds light on neuronal regeneration occurring after injury of the olfactory epithelium.
authors.affiliation: Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
authors.forename: Estefania
authors.initials: E
authors.lastname: Lopez-Arenas
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
authors.forename: Juan
authors.initials: J
authors.lastname: Bacigalupo
authors.forename: Lorena
authors.initials: L
authors.lastname: Sulz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000187:drug effects; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D052247:Nitric Oxide Synthase Type II