OPTN knockout alleviates OVA-induced airway inflammation in a mouse model of asthma

Asthma is a common inflammatory disease of the respiratory system. This study aimed to investigate the effect of optineurin (OPTN) gene knockout on airway inflammation in an ovalbumin (OVA)-induced asthma mouse model.

An OVA-induced chronic asthma model was established in 6-8-week-old C57BL/6 wild-type and OPTN knockout mice. Lung inflammation and goblet cell hyperplasia were respectively evaluated by hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Levels of epithelial-derived alarmins (IL-33, TSLP, and IL-25), Th2 cytokines (IL-4, IL-5, and IL-13), and serum immunoglobulin E (IgE) were measured by enzyme-linked immunosorbent assay (ELISA). To further assess autophagic flux, additional experimental groups treated with the lysosomal inhibitor chloroquine were included, and autophagy-related markers were examined by immunohistochemistry and Western blotting.

Histological analyses demonstrated that OPTN deficiency markedly attenuated OVA-induced asthma-like airway inflammation, as evidenced by reduced inflammatory cell infiltration, basement membrane thickening, goblet cell hyperplasia, and mucus secretion. ELISA results showed that serum IgE levels, the concentrations of alarmins and inflammatory cytokines in bronchoalveolar lavage fluid were significantly decreased in the OPTN^⁻/⁻ group compared with the wild-type group. Furthermore, immunohistochemical and Western blot analyses revealed altered expression of the autophagy-related markers LC3 and p62 in OPTN-deficient lungs. The chloroquine treatment experiment suggested that OPTN might be involved in the regulation of autophagy in the lungs, but the relevant difference did not reach statistical significance.

OPTN knockout effectively alleviates asthma-like airway inflammation, and the underlying mechanism may be associated with the regulation of autophagy.