Mycoplasma pneumoniae downregulates RECK to promote matrix metalloproteinase-9 secretion by bronchial epithelial cells. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Qin, Lianmei; Liu, Lu; Wu, Yueping; Chen, Yiwen; Wu, Yueyue; Luo, Haodang; Xi, Yixuan; Xiu, Feichen; Hu, Jun; Chen, Liesong; Wu, Ning; He, Jun; Zeng, Yanhua; Zhu, Cuiming; You, Xiaoxing
• Is Part Of: Virulence. Volume 13:Issue 1(2022)
• Page Start: 1270
• Page End: 1284
• Publication Date: 2022-12-31
• Subjects: Mycoplasma pneumoniae -- matrix metalloproteinase-9 -- reversion-inducing cysteine-rich protein with Kazal motifs (RECK) -- bronchial epithelial cell; Virulence (Microbiology) -- Periodicals; Bacterial diseases -- Periodicals; Molecular microbiology -- Periodicals; 579.05
• DOI: 10.1080/21505594.2022.2101746
• Languages: English
• ISSNs: 2150-5608

Abstract

ABSTRACT: Airway epithelial cells function as both a physical barrier against harmful substances and pathogenic microorganisms and as an important participant in the innate immune system. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in modulating inflammatory responses during respiratory infections. However, the signalling cascade that induces MMP-9 secretion from epithelial cells infected with Mycoplasma pneumoniae remains poorly understood. In this study, we investigated the mechanism of MMP-9 secretion in airway epithelial cells infected with M. pneumoniae . Our data clearly showed that M. pneumoniae induced the secretion of MMP-9 from bronchial epithelial cells and upregulated its enzymatic activity in a time- and dose-dependent manner. Using specific inhibitors and chromatin co-precipitation experiments, we confirmed that the expression of MMP-9 is reliant on the activation of the Toll-like receptor 2 (TLR2) and TLR6-dependent mitogen-activated protein kinase/nuclear factor- κB/activator protein-1 (MAPK/NF-κB/AP-1) pathways. Additionally, epigenetic modifications such as histone acetylation and the nuclear transcription factor Sp1 also regulate MMP-9 expression. M. pneumoniae infection also decreased the expression of the tumour suppressor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) by inducing Sp1 phosphorylation. Overexpression of RECK significantly impaired the M. pneumoniae -triggered increase in MMP-9 enzymatic activity, although the level of MMP-9 protein remained constant. The study demonstrated that M. pneumoniae -triggered MMP-9 expression is modulated by TLR2 and 6, the MAPK/NF-κB/AP-1 signalling cascade, and histone acetylation, and M. pneumoniae downregulated the expression of RECK, thereby increasing MMP-9 activity to modulate the inflammatory response, which could play a role in airway remodelling.