House dust mite allergen induces inflammasome activation and NFkB signal transduction in monocytes

Abstract

Abstract Over the past few decades, allergic diseases have become increasingly prevalent worldwide. House dust mite (HDM) is the most important domestic source for allergic diseases such as allergic rhinitis, asthma and atopic dermatitis. Dermatophagoides pteronyssinus (Der p) is the major environmental allergen in southeast Asia because of the humid and warm environment is suitable for its growth. Der p has been identified which could increase proinflammatory cytokine expression through activating innate immune response. Inflammasomes activation was reported which could help host defense pathogens and allergen in the recent years. However, the correlation between HDM induced allergic inflammation and inflammasomes activation remains unclear. The aim of this study was to investigate the effect of HDM allergen on inflammasomes activation and downstream signal transduction. We found that THP-1 cells, stimulated with HDM crude extract, activated NALP1, NLRC4, NLRP3 and AIM2 inflammasomes in a time-dependent manner. The expression of adaptor protein ASC and its caspase effector, Caspase-1, as well as proinflammatory cytokines, IL-1β, IL-6, IL-8 and TNF-α were significantly upregulated after HDM stimulation. Mechanistic study revealed that HDM stimulation increased the expression of phosphorylated NFkB, JNK and AKT. Our study suggests that HDM allergen could induce inflammatory response through NFkB signal transduction pathway and inflammasomes activation. Thus, we could use these data for developing specific target immunotherapy in the future.