Elevated IL-33 promotes expression of MMP2 and MMP9 via activating STAT3 in alveolar macrophages during LPS-induced acute lung injury

• Published in: Cellular & molecular biology letters 2018-10, Vol.23 (1), p.52-52, Article 52
• Main Authors: Liang, Yafeng, Yang, Nengli, Pan, Guoquan, Jin, Bingxin, Wang, Shufen, Ji, Wei
• Format: Article
• Language: English
• Subjects: Acute lung injury (ALI); Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Animals; Cells, Cultured; Disease Models, Animal; Gene Knockdown Techniques; IL-33; Inflammation Mediators - metabolism; Interleukin-33 - metabolism; Lipopolysaccharides; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - pathology; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; MMP2; MMP9; Neutralization Tests; Rats, Wistar; STAT3; STAT3 Transcription Factor - metabolism; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1425-8153; 1689-1392
• DOI: 10.1186/s11658-018-0117-x

Pulmonary inflammation and endothelial barrier permeability increase in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by pro-inflammatory cytokines and matrix metalloproteinases (MMPs). However, the relationship between pro-inflammatory cytokines and MMPs in ALI/ARDS remains poorly understood. A lipopolysaccharide (LPS)-induced ALI rat model was established through intratracheal instillation. The wet/dry ratios of lung tissues were measured, and bronchoalveolar lavage fluid (BALF) was collected to test protein concentrations, total cell/macrophage numbers, and pro-inflammatory cytokine levels. LPS-treated alveolar macrophages were utilized in in vitro experiments. The expression and secretion of MMPs were respectively detected using quantitative PCR, Western blotting and ELISA assays. The levels of IL-33 and MMP2/9 in BALF increased in all the ALI rats with severe lung injury. LPS-induced IL-33 autocrine upregulated the expression of MMP2 and MMP9 through activating STAT3. Neutralizing IL-33 in culture medium with specific antibodies suppressed the expression and secretion of MMP2 and MMP9 in LPS-treated alveolar macrophages. Consistently, eliminating IL-33 decreased the levels of MMP2 and MMP9 in BALF and alleviated lung injury in ALI rats. The IL-33/STAT3/MMP2/9 regulatory pathway is activated in alveolar macrophages during acute lung injury, which may exacerbate the pulmonary inflammation.