NLRP3 inhibition attenuates the allergic rhinitis symptoms in a mouse model.

Abstract

Background: Recent human and animal studies have demonstrated that Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is closely involved in the development of allergic diseases.

Objective: To identify the mechanism underlying the activation of NLRP3 inflammasome signaling pathway in an ovalbumin (OVA)-induced allergic rhinitis (AR) mice model and to validate the effect of a specific inhibitor of the NLRP3, MCC950.

Methods: Mice were divided into three groups and each group consisted of ten mice (saline group, the negative control group; OVA group, the OVA-induced AR model group; and OVA+MCC group, treated with 10 mg/kg MCC950). MCC950 was administered intraperitoneally every second day. Multiple parameters of AR, including NLRP3, caspase-1, interleukin (IL)-1β, and IL-18 were evaluated by using ELISA, RT-qPCR, histopathology, and immunohistochemistry.

Results: The mRNA and protein levels of NLRP3, caspase-1, IL-1β and IL-18 were upregulated in the OVA group compared with those of the saline group. MCC950 significantly inhibited the mRNA and protein levels of NLRP3, caspase-1, IL-1β and IL-18 in nasal tissue. Further, AR symptoms and eosinophil count were normalized after MCC950 treatment. However, OVA-specific IgE was not restored in the OVA+MCC group.

Conclusion: NLRP3 inflammasome signaling pathway may be an alternative pathway to induce AR symptoms in OVA-induced AR model. MCC950 is a specific inhibitor of NLRP3 cascade, which attenuates AR symptoms regardless of IgE.