Pro-inflammatory cytokines modify neuronal nicotinic acetylcholine receptor assembly

• Published in: Journal of neuroimmunology 2005-09, Vol.166 (1), p.88-101
• Main Authors: Gahring, Lorise C., Days, Emily L., Kaasch, Tuesday, González de Mendoza, Mónica, Owen, Leah, Persiyanov, Karina, Rogers, Scott W.
• Format: Article
• Language: English
• Subjects: Animals; Assembly; Cells, Cultured; Cytokine; Humans; Inflammation; Inflammation Mediators - physiology; Interleukin-1 - pharmacology; Interleukin-1 - physiology; Interleukin-1β; Mice; Neurons - metabolism; Nicotinic receptors; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Processing, Post-Translational - drug effects; Protein Processing, Post-Translational - physiology; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; Recombinant Proteins - pharmacology; Transfection; Tumor necrosis factor α; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2005.05.007

We have examined the impact of the inflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) on assembly of nAChRs from subunit mixtures of nAChRα4, β2 and β4 transiently transfected into 293 cells. In control transfections approximately 55% of α4 associated preferentially with β4, but less than 15% complexed with β2 and the remainder was associated with both β subunits. These relative ratios were modified by pro-inflammatory cytokines. IL-1β strongly enhanced α4/β2 association and decreased α4/β4, whereas TNFα promoted mixed α4/β2/β4 interactions. These results show that the emerging rules governing assembly of nAChRs are subject to modification by the pro-inflammatory cytokine environment.