Pro-inflammatory cytokines modify neuronal nicotinic acetylcholine receptor assembly

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.