Alpha-MSH inhibits inflammatory signalling in olfactory ensheathing cells.
Alpha-melanocyte stimulating hormone (alpha-MSH) was originally documented as a peptide that induced pigmentation in skin. However, more recent work suggests that it acts as a potent anti-inflammatory molecule in several tissues including nerve. Alpha-MSH works by directly inhibiting cytokines that cause inflammation, in particular tumour necrosis factor-alpha, interleukin-1beta, interleukin-6 and gamma-interferon. A common mechanism of inhibition is via the NF-kappaB transcription factor. We investigated the ability of alpha-MSH to inhibit the activation of NF-kappaB in cultured rat primary olfactory ensheathing cells stimulated with tumour necrosis factor-alpha or gamma-interferon. Both cytokines activated NF-kappaB rapidly (after 60 min incubation), observed as a translocation from cytoplasm to nucleus. alpha-MSH inhibited this activation (and hence nuclear translocation) by approximately 50% for both cytokines. The anti-inflammatory properties of this peptide in neural cells may therefore support a basis for treating CNS injury, where inflammation is a major problem.
Teare
Katrina A
KA
University of Nottingham, Department of Tissue Engineering and Drug Delivery, Nottingham, UK.
Pearson
Richard G
RG
Shakesheff
Kevin M
KM
Raisman
Geoff
G
Haycock
John W
JW
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000502:physiology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009830:Olfactory Bulb / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000521:alpha-MSH / Q000502:physiology*
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; D007371:Interferon-gamma