SerpinA3n affects ovalbumin (OVA)-induced asthma in neonatal mice via the regulation of collagen deposition and inflammatory response.

OBJECTIVE: To investigate the effects of serine protease inhibitor 3n (SerpinA3n) in a neonatal mouse model of asthma. METHODS: The study utilized a neonatal mouse ovalbumin (OVA) sensitization model of asthma. Wild type (WT) and SerpinA3n-/- mice were randomly divided into WT/SerpinA3n-/- + saline, WT/SerpinA3n-/- + OVA, WT/SerpinA3n-/- + OVA + rSerpinA3n (recombinant mouse SerpinA3n protein), and WT/SerpinA3n-/- + OVA + DEX (dexamethasone, positive control) groups followed by hematoxylin-eosin (HE) staining, Masson's trichrome stainings, Sircol soluble collagen assay, quantitative real time polymerase chain reaction (qRT-PCR), Western Blot and enzyme linked immunosorbent assay (ELISA). RESULTS: OVA-induced neonatal mice showed the increases in airway hyper-reactivity with the up-regulated total cells, eosinophil, lymphocyte and neutrophil in bronchoalveolar lavage fluid (BALF), which was much higher in WT + OVA + rSerpinA3n group (P < 0.05). SerpinA3n-/- suppressed the serum concentrations of total immunoglobulin E (IgE) and OVA-specific IgG1 in OVA-induced asthmatic mice, and alleviated the pathological changes of lung tissues, which was reversed by rSerpinA3n injection (P < 0.05). Besides, WT + OVA group showed more severe in collagen deposition in lung tissues than SerpinA3n-/- + OVA group with increased expression of matrix metallopeptidase-2 (MMP-2), MMP-9, Eotaxin-1, Interleukin 5 (IL-5), IL-13 and IL-4 in lung tissues and deceased IL-10 and Interferon-gamma (IFN-I³) (P < 0.05). Nevertheless, the ameliorating effects of SerpinA3n knockout on OVA-induced asthmatic mice can be reversed by rSerpinA3n. CONCLUSION: SerpinA3n knockout can attenuate airway hyper-reactivity, mitigate inflammatory responses and reduce collagen deposition in lung tissues of neonatal mice with asthma.