Pseudomonas aeruginosa accentuates epithelial-to-mesenchymal transition in the airway

Abstract

Epithelial-to-mesenchymal transition (EMT) has been implicated in the dysregulated epithelial wound repair that contributes to obliterative bronchiolitis (OB) after lung transplantation. Acquisition of Pseudomonas aeruginosa in the transplanted airway has been shown to be a risk factor for the development of OB. We investigated the potential of P. aeruginosa to drive EMT in primary bronchial epithelial cells (PBECs) isolated from lung transplant recipients.Changes in the expression of epithelial and mesenchymal markers was assessed in cells challenged with clinical isolates of P. aeruginosa or co-cultured with P. aeruginosa-activated monocytic cells (THP-1) in the presence or absence of transforming growth factor (TGF)-b1.P. aeruginosa did not drive or accentuate TGF-b1-driven EMT directly. Co-culturing P. aeruginosa-activated THP-1 cells with PBECs did not drive EMT. However, co-culturing P. aeruginosa-activated THP-1 cells with PBECs significantly accentuated TGF-b1-driven EMT.P. aeruginosa, via the activation of monocytic cells, can accentuate TGF-b1-driven EMT. These in vitro observations may help explain the in vivo clinical observation of a link between acquisition of P. aeruginosa and an increased risk of developing OB.

Transforming Growth Factor-β1 (TGF-β1) Driven Epithelial to Mesenchymal Transition (EMT) is Accentuated by Tumour Necrosis Factor α (TNFα) via Crosstalk Between the SMAD and NF-κB Pathways

“…Recently TNFα has been shown to accentuate TGF-β1 driven EMT in a range of cell types highlighting a potential link between EMT and inflammation [17][18][19][20][21][22][23]. However, the mechanisms responsible have been ill-defined and further studies are required to elucidate the signalling pathways involved so potential therapeutic targets to limit or even reverse inflammatory driven EMT can be identified.…”

“…Pseudomonas aeruginosa whole cell lysate was prepared from a laboratory reference strain (NCTC10662) as previously described [23,24]. Briefly, the strain was grown overnight on 1% horse blood agar plates, harvested into PBS and standardised to 0.2 at an optical density of 600 nm.…”

Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype

“…Bacterial infection with Pseudomonas aeruginosa has been shown to significantly increase inflammation in lung transplant recipients [167]. BORTHWICK et al [168] have shown that bacteria are able to induce EMT in the presence of TGF-b. This effect is indirect and due to the activation of immune cells [168].…”

“…BORTHWICK et al [168] have shown that bacteria are able to induce EMT in the presence of TGF-b. This effect is indirect and due to the activation of immune cells [168]. It would be interesting to investigate whether infection with cytomegalovirus, which constitutes a risk factor for BO, can induce EMT.…”

Role of the transforming growth factor (TGF)-β1 and TGF-β1 signaling pathway on the pathophysiology of respiratory pneumococcal infections

“…The recognition of microbial factors stimulates the cells to produce other PRRs, acute phase proteins and cytokines, to recognize the microbes more efficiently, inhibit bacterial growth, recruit inflammatory cells to the site of infection, and to enhance the phagocytic activity [24]. Alveolar epithelium expresses TGF-β1, which is upregulated further upon an infection with respiratory bacterial pathogens, including Mycobacterium tuberculosis (M. tuberculosis) [27][28][29], Pseudomonas aeruginosa [30][31][32][33], nontypeable Haemophilus influenzae (NTHi) [34][35][36], and pneumococcus [35,37].…”