Role of IL33/HIF1α/VEGF in intermittent hypoxia-induced lung injury

To investigate the role of IL33/HIF1α/VEGF in lung tissue injury caused by intermittent hypoxia (IH) model in mice, and to reveal its possible mechanisms.

Forty male C57BL/6 J mice were randomly divided into the room air (RA) group, the intermittent hypoxia (IH) group, the intermittent hypoxia + IL33 neutralizing antibody (IH-antiIL33) group, the intermittent hypoxia + IL33 recombinant mouse protein (IH-rmIL33) group and the intermittent hypoxia + IgG negative control (IH-IgG) group. The following parameters were evaluated in all mouse groups:pulmonary function and lung tissue histology and molecular profiles (mRNA/protein levels of IL-33, HIF-1α, and VEGF, along with inflammatory factor concentrations).

Pulmonary function tests demonstrated significantly aggravated airway obstruction in the IH group compared to the RA group (P < 0.01). IL-33 intervention primarily affected small airway resistance and expiratory function in IH mice (P < 0.05). Histological staining revealed that rmIL-33 exacerbated IH-induced lung tissue injury and fibrosis (P < 0.01), while anti-IL-33 intervention showed alleviating effects. Molecular analyses confirmed upregulation of IL-33, HIF-1α, VEGF, and inflammatory factors (IL-6, TNF-α) in IH group lung tissues (P < 0.01). Exogenous IL-33 further enhanced these expression levels (P < 0.05), whereas anti-IL-33 intervention effectively suppressed them (P < 0.01). IHC results indicated significant alterations in IL-33 protein expression following interventions (P < 0.001). STRING database predictions suggested potential indirect interaction between IL-33 and HIF-1α via IL1R1.

It is suggested that IL33/HIF1α/VEGF may be involved in the pathogenesis of lung injury due to IH through multiple mechanisms.