Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 29, Issue 1, Pages 152-157Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2015.06.034
Keywords
Nicotinic receptors; Acetylcholine; Pro-inflammatory cytokines; Multiple sclerosis
Categories
Funding
- FISM - Fondazione Italiana Sclerosi Multipla [2013/R/25]
- FISM project [2013/R/25]
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Acetylcholine (ACh) and its receptors of muscarinic and nicotinic types are involved in the modulation of immune and inflammatory responses. In present work we have characterized the nicotinic receptors expression in PBMC of RR-MS patients and healthy donors (HD) and their ability to modulate pro-inflammatory cytokines. Here we report that the IL-1 beta e IL-17 levels are significantly increased in serum of RR-MS patients in respect to HD and that the PBMC stimulation with PHA caused a significant increase in pro-inflammatory cytokine levels both in RR-MS and HD subjects, with higher increase of protein release in RR-MS patients than in HD. The PBMC treatment with PHA plus nicotine produced a significant decrease of IL-1 beta e IL-17 both as transcript and as protein, confirming that the PBMC of the patients respond to the cholinergic stimulation more than PBMC of HD. By real time PCR and western blot analysis we have also demonstrated that in particular ea receptor subtype appeared expressed at comparable levels both in RR-MS patients and HD. The PHA stimulation results to inhibit the alpha 7 subunit expression while the nicotine causes a significant increase in alpha 7 transcripts but only in MS patients. The data obtained highlight the role of alpha 7 receptor subtype in the modulation of anti-inflammatory cytokines also in MS. Moreover the ability of nicotine to up-regulate the expression of alpha 7 receptor subtype in RR-MS patients, indicates that nicotinic receptor stimulation may contribute to down-modulate the inflammation occurred in MS by a positive feedback control of its expression. (C) 2015 Elsevier B.V. All rights reserved.
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