Downregulation of α7 nicotinic acetylcholine receptors in peripheral blood monocytes is associated with enhanced inflammation in preeclampsia

Abstract

Background: Preeclampsia is associated with chronic inflammation. The cholinergic anti-inflammatory pathway regulates systemic inflammation through activating α7 nicotinic acetylcholine receptors (α7nAChR) expressed in monocytes/macrophages. This study aimed to investigate the role of α7nAChR in peripheral blood monocytes in preeclampsia. Methods: Peripheral blood monocytes were isolated from 30 nonpregnant (NP), 32 normotensive pregnant (NT), and 35 preeclamptic (PE) women. Results: We found that both protein and mRNA expression levels of α7nAChR in monocytes from the PE women were significantly lower than those of the NP and NT women (both p < 0.01). α7nAChR protein expression levels in monocytes were negatively correlated with levels of systolic blood pressure (r = - 0.40, p = 0.04), proteinuria (r = - 0.54, p < 0.01), tumor necrosis factor-alpha (TNF-α, r = - 0.42, p = 0.01), and interleukin (IL)-1β (r = - 0.56, p < 0.01), while positively correlated with IL-10 levels (r = 0.43, p = 0.01) in the PE women. Both baseline and lipopolysaccharides (LPS)-induced increase of TNF-α, IL-1β, and IL-6 levels from monocytes were higher in the PE group than the NP and NT groups (all p < 0.01), but IL-10 levels in the PE group was lower than that of the NP and NT groups (p < 0.01). In addition, the NF-κB activity in monocytes from the PE women was higher than the NP and NT women (p < 0.01). Importantly, activation of α7nAChR with its agonist PNU-282987 inhibited NF-κB, decreased TNF-α, IL-1β, and IL-6 release, and increased IL-10 release in monocytes from the PE women (all p < 0.01). Conclusion: In conclusion, these findings suggest that downregulation of α7nAChR may be associated with the development of preeclampsia through increasing pro-inflammatory and decreasing anti-inflammatory cytokine release via the NF-κB pathway.