IL‐33/ST2 axis deficiency exacerbates neutrophil‐dominant allergic airway inflammation

Abstract

Objective The IL‐33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL‐33/ST2 axis in neutrophil‐dominant allergic airway inflammation. Methods House‐dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil‐dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL‐33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow‐derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. Results In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL‐33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL‐33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil‐dominant allergic airway inflammation in an HDM/LPS‐induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL‐33‐ or ST2‐deficient mice tended to produce higher levels of the neutrophilic chemokine KC. Conclusions These results demonstrated that the IL‐33/ST2 axis may play a protective role in neutrophil‐dominant allergic airway inflammation.

Effects of SPA4 peptide on lipopolysaccharide‐disrupted lung epithelial barrier, injury, and function in a human cell system and mouse model of lung injury

“…Furthermore, our results revealed that the SPA4 peptide restores the LPS-disrupted TEER by mainly affecting the subcellular distribution of tight junction proteins (Figure 3). Similarly, changes in localization pattern, but no effect on expression levels of occludin, have been reported earlier in human bronchial epithelial cells challenged with E. coli O111:B4-derived LPS, pollutants, and cigarette smoke, through hyperphosphorylation of occludin (Cao et al, 2015;Ma et al, 2021). Similarly, tyrosine phosphorylation of ZO-1, occludin, and E-Cadherin results in their re-distribution at a cellular level (Samak et al, 2014).…”

Matrix metalloproteinase 9: An emerging biomarker for classification of adherent vestibular schwannoma

“…The effect of TNF-α stimulation was inhibited by subsequent addition of MMP9 inhibitors (SB-3CT or MMP9-IN-I) or silvestrol ( Figure 5H and Supplementary Figure 6F and -G ). 46 , 47 As a positive control, HEI-193 cells invaded through collagen-I with recombinant MMP9, an effect that was inhibited with MMP inhibitors and silvestrol ( Figure 5J ). Similar results were observed in MD-MSCs ( Supplementary Figure 6 ).…”

IL-24 Contributes to Neutrophilic Asthma in an IL-17A-Dependent Manner and Is Suppressed by IL-37

“…The present asthma model was developed according to previous methods. 19 20 Briefly, mice were sensitized intranasally (i.n.) using HDM (25 μg/mouse, cat# XPB82D3A25; Greer, London, USA) with or without LPS (10 μg/mouse, E. coli serotype O111: B5, cat# L2880, Sigma-Aldrich, St. Louis, MO, USA) dissolved in 20 μL of PBS once daily on days 0, 1, and 2; then, challenged with HDM (25 μg/mouse) alone i.n.…”