Fig. 5. Activation of inflammatory pathways by Aβ1–42 through the α7 nicotinic acetylcholine receptor is mitigated by CHRFAM7A.
a Comparison of inflammasome-related gene expression profiles in neuronal progenitor cells (NPCs) generated from UB068 and UB052 (left panel) and in UB068 transfected with CHRFAM7A and/or empty vector (EV) (right panel). Data are presented as mean ± SEM. * - P < 0.05 - difference in gene expression levels in UB052 cells compared to UB068 and in CHRFAM7A-transfected cells compared to EV-transfected cells. b Pretreatment with α7-selective antagonist methyllycaconitine (MLA) decreases Aβ1–42-induced IL-1β (left panel) and tumor necrosis factor α (TNF-α; right panel) expression in UB068 and UB052 lines. 100 nM Aβ1–42 was used for treatment. Data are presented as mean ± SEM. *P < 0.05—difference in Aβ1–42-induced gene expression levels between MGE progenitors with and without treatment with MLA in both cell lines. c Expression of IL-1β (left panel) and TNF-α (right panel) correlates with Aβ1–42 uptake in concentration-dependent manner in the NPCs transfected with CHRFAM7A. Data are presented as mean ± SEM. *P < 0.05—difference in IL-1β and/or TNF-α expression in CHRFAM7A-transfected cells compared to EV-transfected cells at each given Aβ1–42 concentration. d Representative confocal images and e immunoblot analysis of total cell lysates showing an increase in IL-1β expression in the cells transfected with CHRFAM7A. f In MGE progenitors transfected with CHRFAM7A, Fluorescin-Aβ1–42 uptake induces a concentration-dependent increase in IL-1β secretion as detected by ELISA. Data are presented as mean ± SD. *P < 0.05—difference between IL-1 β concentration in CHRFAM7A-transfected cells compared to EV-transfected cells at each given Aβ1–42 concentration