Alpha-MSH inhibits inflammatory signalling in Schwann cells

Peripheral nervous system injury may be corrected by surgical repair, but in many cases this is not possible and will result in loss of motor and sensory function. Schwann cells provide many neurotrophic signals essential for axon regeneration and immediately after injury inflammatory cytokines are released necessary for Schwann cell de-differentiation. However, extended periods of inflammation after injury prevent Schwann cell proliferation, and therefore interventional approaches to enhance proliferation may in turn improve axon regeneration. We therefore investigated the ability of alpha-melanocyte stimulating hormone (alpha-MSH; a potent anti-inflammatory peptide) to inhibit the activation of the NF-kappaB transcription factor (required for inflammatory signalling) in cultured rat primary Schwann cells, stimulated with tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma). Both cytokines activated NF-kappaB rapidly after 60 min incubation, observed as a translocation from the cytoplasm to the nucleus. alpha-MSH inhibited activation (i.e. inhibited nuclear translocation) in response to TNF-alpha or IFN-gamma by 81% and 100% respectively. The anti-inflammatory properties of this peptide may therefore have potential for treatment of peripheral nerve injury to improve the healing response.