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Lack of galectin‐3 speeds W allerian degeneration by altering TLR and pro‐inflammatory cytokine expressions in injured sciatic nerve
Author(s) -
Mietto Bruno Siqueira,
Jurgensen Sofia,
Alves Lucinéia,
Pecli Cyntia,
Narciso Marcelo Sampaio,
AssunçãoMiranda Iranaia,
VillaVerde Dea Maria Serra,
Souza Lima Flávia Regina,
Menezes João Ricardo Lacerda,
Benjamim Cláudia Farias,
Bozza Marcelo Torres,
Martinez Ana Maria Blanco
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12161
Subject(s) - cytokine , sciatic nerve , microbiology and biotechnology , inflammation , galectin , immunology , degeneration (medical) , neuroscience , medicine , biology , anatomy , pathology
Wallerian degeneration ( WD ) comprises a series of events that includes activation of non‐neuronal cells and recruitment of immune cells, creating an inflammatory milieu that leads to extensive nerve fragmentation and subsequent clearance of the myelin debris, both of which are necessary prerequisites for effective nerve regeneration. Previously, we documented accelerated axon regeneration in animals lacking galectin‐3 ( G al‐3), a molecule associated with myelin clearance. To clarify the mechanisms underlying this enhanced regeneration, we focus here on the early steps of WD following sciatic nerve crush in G al‐3 −/− mice. Using an in vivo model of nerve degeneration, we observed that removal of myelin debris is more efficient in G al‐3 −/− than in wild‐type ( WT ) mice; we next used an in vitro phagocytosis assay to document that the phagocytic potential of macrophages and S chwann cells was enhanced in the G al‐3 −/− mice. Moreover, both RNA and protein levels for the pro‐inflammatory cytokines IL ‐1β and TNF ‐α, as well as for T oll‐like receptor ( TLR )‐2 and ‐4, show robust increases in injured nerves from G al‐3 −/− mice compared to those from WT mice. Collectively, these data indicate that the lack of G al‐3 results in an augmented inflammatory profile that involves the TLR –cytokine pathway, and increases the phagocytic capacity of Schwann cells and macrophages, which ultimately contributes to speeding the course of WD .