Recombinant pyrin domain protein attenuates allergic inflammation by suppressing NF-κB pathway in asthmatic mice

Abstract

Pyrin domain (PYD), a subclass of protein motif known as the death fold, is frequently involved in inflammation and immune responses. PYD modulates nuclear factor-kappa B (NF-κB) signalling pathway upon various stimuli. Herein, a novel recombinant pyrin domain protein (RPYD) was generated. Its role and mechanism in inflammatory response in an ovalbumin (OVA) induced asthma model was investigated. After OVA challenge, there was inflammatory cell infiltration in the lung, as well as airway hyper-responsiveness (AHR) to inhaled methacholine. In addition, eosinophils increased in the bronchoalveolar lavage fluids, alone with the elevated levels of Th-2 type cytokines [interleukin (IL)-4, IL-5 and IL-13], eotaxin, and adhesion molecules. However, the transnasal administration of RPYD before the OVA challenge significantly inhibited these asthmatic reactions. Moreover, RPYD markedly suppressed NF-κB translocation, reduced phosphorylation of p38 MAPK, and thus attenuated the expression of intercellular adhesion molecule 1 and IL-6 in the BEAS-2B cells stimulated by proinflammatory cytokines in vitro. These findings indicate that RPYD can protect asthma host from OVA-induced airway inflammation and AHR via down-regulation of NF-κB and p38 MAPK activities. RPYD may be used as a potential medicine for the treatment of asthma in clinic.

Keywords: NF‐κB Pathway; allergic inflammation; asthma; pyrin domain protein.