Upregulation of Toll-like receptors after nerve injury and inflammatory signaling from Wallerian degeneration

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Název česky Upregulace Toll-like receptorů a zánětová signalizace Wallerovy degenerace po poškození nervu


Rok publikování 2015
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Lékařská fakulta

Popis Aim. Wallerian degeneration (WD) distal to nerve injury is considered to be aseptic inflammation including fragmentation of axons and their mitochondria, upregulation of ECM molecules and their cleavage. All the products of WD named as damage associated molecular patterns (DAMPs) can be released into blood circulation and reach to remote structures without blood barriers. Here, DAMPs are detected by Toll-like receptors (TLRs) that mediate inflammatory reaction. We hypothesize that upregulation of TLRs is responsible for inflammatory reactions in the dorsal root ganglia (DRG) both associated and non-associated with injured nerve. Methods. The right sciatic nerve of adult rats was crushed (n=15), ligated (n=15) or transected (n=15) and animals were left to survive for 1, 3, 7, 14 and 21 days. The sciatic nerve and DRG of naive rats (n=6) and sham-operated rats (n=6) were used as controls. TLR2, 3, 4, and 9 were detected by standard indirect immunofluorescence in the cryostat sections through distal and proximal nerve stumps as well as contralateral sciatic nerve. In addition, bilateral DRG of L4-L5 and C7-C8 segments were used for TLRs detection. Activated Schwann or satellite glial cells were identified by co-localization with monoclonal S100 antibody. In addition, we tested upregulation of TLR9 in Schwannoma cells (RT4) by N-formyl-methionyl-leucyl-phenylalanine (fMLF), the prototypical N-formylated peptide released by fragmented mitochondria. Results. Sciatic nerve injuries induced upregulation of investigated TLRs in Schwann cells distal and proximal as well as in neurons and satellite glial cells of DRG from ipsilateral and contralateral sides. Schwann cells cultivated in medium supplied with fMLP displayed an increased expression of TLR9 in endosomes and patches of plasma membrane particularly in cytoplasmic processes or small protrusions. Medium containing fMLP also induced increase of NF-kappa B, TNF alpha and IL1beta. Conclusion. Our results shown that TLRs are upregulated in Schwann cells activated by nerve injury and in DRG not only associated, but also non-associated with injured nerve. The increased expression of TLRs can be regulated by DAMPs that are responsible for dissemination of inflammatory reactions into remote nervous structures.
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