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

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.