To explore the role of granzyme B in PM_2.5 promoting the expression of inflammatory cytokines in natural killer (NK) cells.

First, the PM_2.5 dose gradient was set. The experiment was divided into blank control group (0 μg/ml), PM_2.5 group (50 μg/ml), PM_2.5 group (150 μg/ml), and PM_2.5 group (450 μg/ml). By setting the PM_2.5 dose gradient, we observed the correlation between the expression of NK cell granzyme B and inflammatory cytokines TNF-α and IL-1β. Second, in order to determine whether granzyme B plays a promoting role in the expression of inflammatory cytokines in NK cells promoted by PM_2.5, the experiment was divided into blank control group, Serpina3n group, PM_2.5 group and Serpina3n+ PM_2.5 group according to whether PM_2.5 exposure and Serpina3n inhibitor were pretreated. Serpina3n group and Serpina3n+ PM_2.5 group were added Serpina3n(100 ng/ml) 1 hour before PM_2.5 poisoning. Third, in order to determine whether granzyme B plays a role through IL-18 in PM_2.5 promoting the expression of inflammatory cytokines in NK cells, the experiment was divided into blank control group, IL-18BP, PM_2.5 group, and IL-18BP+ PM_2.5 group according to whether PM_2.5 exposure and IL-18BP inhibitor were pretreated. One hour before PM_2.5 exposure, IL-18BP group and IL-18BP+ PM_2.5 group were added with IL-18BP (100 ng/ml). The expression of NK cell protein and the levels of TNF-α and IL-1β in cell culture medium were detected in each group separately.

PM_2.5 promoted the expression of granzyme B and inflammatory factors TNF-α and IL-1β in NK cells. Blocking granzyme B inhibited IL-18 expression and NF-κB phosphorylation, and decreased TNF-α and IL-1β expression in NK cells. Blocking IL-18 inhibited the phosphorylation of NF-κB and decreased the expression of TNF-α and IL-1β.

PM_2.5 may promote the expression of TNF-α and IL-1β in NK cells by activating granzyme B/IL-18 signaling pathway, and the mechanism may be related to the activation of NF-κB signaling pathway.