Pro-inflammatory cytokines modify neuronal nicotinic acetylcholine receptor assembly.
We have examined the impact of the inflammatory cytokines interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) on assembly of nAChRs from subunit mixtures of nAChRalpha4, beta2 and beta4 transiently transfected into 293 cells. In control transfections approximately 55% of alpha4 associated preferentially with beta4, but less than 15% complexed with beta2 and the remainder was associated with both beta subunits. These relative ratios were modified by pro-inflammatory cytokines. IL-1beta strongly enhanced alpha4/beta2 association and decreased alpha4/beta4, whereas TNFalpha promoted mixed alpha4/beta2/beta4 interactions. These results show that the emerging rules governing assembly of nAChRs are subject to modification by the pro-inflammatory cytokine environment.
Gahring
Lorise C
LC
Salt Lake City VA-Geriatrics Research, Education and Clinical Center, Salt Lake City, UT 84132, USA. Lorise.Gahring@hsc.utah.edu
Days
Emily L
EL
Kaasch
Tuesday
T
González de Mendoza
Mónica
M
Owen
Leah
L
Persiyanov
Karina
K
Rogers
Scott W
SW
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D018836:Inflammation Mediators; D007375:Interleukin-1; D020033:Protein Isoforms; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha