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Laminin activates NF-kappaB in Schwann cells to enhance neurite outgrowth.
Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy. Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Hand Surgery.
2008 (English)In: Neuroscience Letters, ISSN 0304-3940, Vol. 439, no 1, 42-6 p.Article in journal (Refereed) Published
Abstract [en]

Extracellular matrix (ECM) molecules and Schwann cells (SCs) are important components of peripheral nerve regeneration. In this study, the role of the transcription factor nuclear factor kappa B (NF-kappaB) in SC activation in response to laminin and the subsequent effect on in vitro neurite outgrowth was investigated. Immunocytochemistry and Western blot analysis showed that compared with poly-d-lysine (PDL), laminin enhanced the phosphorylation of IkappaB and p65 NF-kappaB signalling proteins in SCs. Phospho NF-kappaB-p65 was localised to the nucleus indicating activation of NF-kappaB. To assess the functional effect of NF-kappaB activation, SCs plated on PDL or laminin were pre-treated with NF-kappaB inhibitors, 6-amino-4-(4-phenoxyphenylethylamino)quinazoline (QNZ) or Z-leu-leu-leu-CHO (MG-132) before NG108-15 neuronal cells were seeded on the SC monolayer. After 24h co-culture in the absence of inhibitors, SCs seeded on laminin enhanced the mean number and length of neurites extended by NG108-15 cells (1.87+/-0.13 neurites; 238.74+/-8.53microm) compared with those cultured in the presence of SCs and PDL (1.26+/-0.07 neurites; 157.57+/-9.80microm). At 72h, neurite length had further increased to 321.83+/-6.60microm in the presence of SCs and laminin. Inhibition of NF-kappaB completely abolished the effect of laminin on SC evoked neurite outgrowth at 24h and reduced the enhancement of neurite length by over 60% at 72h. SC proliferation was unaffected by NF-kappaB inhibition suggesting that the NF-kappaB signalling pathway plays a discrete role in the activation of SCs and their neurotrophic potential.

Place, publisher, year, edition, pages
2008. Vol. 439, no 1, 42-6 p.
URN: urn:nbn:se:umu:diva-19244DOI: 10.1016/j.neulet.2008.04.091PubMedID: 18502047OAI: diva2:201621
Available from: 2009-03-05 Created: 2009-03-05 Last updated: 2009-10-16

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