Olfactory ensheathing cells moderate nuclear factor kappaB translocation in astrocytes.
Nuclear factor kappaB (NFκB) is a key transcriptional regulator of inflammatory genes. We investigated the modulatory effects of olfactory ensheathing cells (OECs), microglia and meningeal fibroblasts on translocation of NFκB to astrocyte nuclei. The percentage of activated astrocytes in co-cultures with OECs was significantly less than for co-cultures with microglia (p<0.001) and fibroblasts (p<0.05). Phorbol myristate acetate (PMA) and calcium ionophore stimulation of p65 NFκB translocation to nuclei provided an in vitro model of astrocyte inflammatory activation. Soluble factors released by OECs significantly moderated the astrocytic NFκB translocation induced by either PMA/calcium ionophore or microglia-derived factors (p<0.001). Insulin-like growth factor-1 may contribute to these effects, since it is expressed by OECs and also significantly moderated the astrocytic NFκB translocation (p<0.05), albeit insufficiently to fully account for the OEC-induced moderation (p<0.01). Olfactory ensheathing cells significantly moderated the increased transcription of the pro-inflammatory cytokine, granulocyte macrophage-colony stimulating factor in the activated astrocytes (p<0.01). These results suggest that transplanted OECs could improve neural repair after CNS injury by moderating astrocyte activation.
Hale
David M
DM
Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7001, Australia.
Ray
Shannon
S
Leung
Jacqueline Y
JY
Holloway
Adele F
AF
Chung
Roger S
RS
West
Adrian K
AK
Chuah
Meng Inn
MI
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D008578:Meninges / Q000166:cytology; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007476:Ionophores; D016328:NF-kappa B; D007334:Insulin-Like Growth Factor I; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium