Pro-inflammatory cytokines are known to have deleterious effects on Schwann cells (SCs). Interleukin 17 (IL-17) is a potent pro-inflammatory cytokine that exhibits relevant effects during inflammation in the peripheral nervous system (PNS), and IL-17-secreting cells have been reported within the endoneurium in proximity to the SCs.
Methods:
Here, we analyzed the effects of IL-17 on myelination and the immunological properties of SCs.
Dorsal root ganglia (DRG) co-cultures containing neurons and SCs from BL6 mice were used to define the impact of IL-17 on myelination and on SC differentiation; primary SCs were analyzed for RNA and protein expression to define the putative immunological alignment of the SCs.
Results:
SCs were found to functionally express the IL-17 receptors A and B. In DRG cultures, stimulation with IL-17 resulted in reduced myelin synthesis, while pro-myelin gene expression was suppressed at the mRNA level.
Neuronal outgrowth and SC viability, as well as structural myelin formation, remained unaffected. Co-cultures exhibited SC-relevant pro-inflammatory markers, such as matrix metalloproteinase 9 and SCs significantly increased the expression of the major histocompatibility complex (MHC) I and exhibited a slight, nonsignificant increase in expression of MHCII, and a transporter associated with antigen presentation (TAP) II molecules relevant for antigen processing and presentation.
Conclusions:
IL-17 may act as a myelin-suppressive mediator in the peripheral nerve, directly propagating SC-mediated demyelination, paralleled by an inflammatory alignment of the SCs.
Further analyses are warranted to elucidate the role of IL-17 during inflammation in the PNS in vivo, which could be useful in the development of target therapies.
Author: Mark StettnerBirthe LohmannKathleen WolfframJan-Philipp WeinbergerThomas DehmelHans-Peter HartungAnne K MausbergBernd C Kieseier
Credits/Source: Journal of Neuroinflammation 2014, 11:63
Published on: 2014-03-29
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