NLRP6 expressed in astrocytes aggravates neurons injury after OGD/R through activating the inflammasome and inducing pyroptosis

Abstract

NLRP6, the nucleotide oligomerization domain-like receptor family pyrin domain containing 6, has a substantiable effect on inflammation and host defense against microorganisms. In our previous study, NLRP6 promotes inflammation after cerebral I/R injury in a MCAO model. However, the effect of NLRP6 in different nerve cells subjected to OGD/R needs to be further understood. Here, evidence shows that the expression of NLRP6 is increased in different nerve cells subjected to OGD/R, and mainly expressed in astrocytes. NLRP6 may up-regulate inflammation factors (IL-1β, Il-8) via the form of inflammasomes in astrocytes after OGD/R. Then, primary neuron-astrocyte co-culture model under OGD/R in vitro was performed, and we found that NLRP6 decreased the neurons viability and aggravated apoptosis of neurons. Mechanically, NLRP6 could induce pyroptosis to regulate the survival of neurons through activating caspase-1.

Keywords: Inflammasomes; Inflammation; NLRP6; OGD/R; Pyroptosis; Stroke.