ANP/NPRA signaling preferentially mediates Th2 responses in favor of pathological processes during the course of acute allergic asthma.

Although atrial natriuretic peptide (ANP) has been well recognized for its role in the regulation of volume-pressure homeostasis in cardiovascular system, its impact on respiratory system, particularly on the pathogenesis of acute allergic asthma, is yet to be elucidated. In the present report, we induced mice with OVA for onset of acute allergic asthma along with the administration of recombinant ANP or A71915 (an antagonist for ANP/natriuretic peptide receptor A, NPRA). It was noted that treatment of mice with ANP significantly promoted inflammatory infiltration in the airway and the production of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) and lung homogenates, and the number of inflammatory cells in the BALF was significantly higher as compared with that of PBS treated asthmatic mice. Moreover, blockade of ANP/NPRA signaling by A71915 almost completely attenuated the effect of ANP administration. Mechanistic studies revealed that ANP repressed the expression of Th1 transcription factor T-bet, but enhanced Th2 transcription GATA3 expression. Together, our data provided feasible evidence suggesting that ANP/NPRA signaling predominantly induces a Th2-type response in favor of pathological processes during the course of acute allergic asthma.