The role of calcium‐sensitive receptor in ovalbumin‐induced airway inflammation and hyperresponsiveness in juvenile mice with asthma

Abstract

Abstract The role of the calcium‐sensitive receptor (CaSR) was assessed in a juvenile mouse model of asthma induced by ovalbumin (OVA). The experiment was divided into normal control, OVA, and OVA +2.5/5 mg/kg NPS2143 (a CaSR antagonist) groups. OVA induction was performed in all groups except the normal control, followed by assessing airway hyperresponsiveness (AHR) and lung pathological changes. Serum OVA‐specific IgE and IgG1 were detected with an enzyme‐linked immunosorbent assay (ELISA), and inflammatory cells were counted in bronchoalveolar lavage fluid (BALF). Real‐time quantitative polymerase chain reaction, ELISA, and western blotting were performed to detect gene and protein expression. NPS2143 improved the OVA‐induced AHR in mice, and AHR was higher in the OVA +2.5 mg/kg NPS2143 group than in the OVA +5 mg/kg NPS2143 group. Furthermore, NPS2143 reduced the production of OVA‐specific IgE and IgG1 in serum and the number of eosinophils and lymphocytes in BALF in OVA mice with reduced CaSR expression in lung tissues. Besides, OVA‐induced mice exhibited peribronchial and perivascular inflammatory cell infiltration, which was accompanied by severe goblet cell hyperplasia/hyperplasia and airway mucus hypersecretion. Furthermore, these mice exhibited increased levels of Interleukin (IL)‐5, IL‐13, MCP‐1, and eotaxin, which were alleviated by NPS2143. The 5 mg/kg NPS2143 showed more effective than the 2.5 mg/kg treatment. CaSR expression was elevated in the lung tissues of OVA‐induced asthmatic juvenile mice, whereas the CaSR antagonist NPS2143 reduced AHR and attenuated the inflammatory response in OVA‐induced juvenile mice, possibly exerting therapeutic effects on childhood asthma.

Keywords

• AHR
• CaSR
• inflammatory response
• NPS2143
• OVA