We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
TLR3 promotes MMP-9 production in primary human airway epithelial cells through Wnt/β-catenin signaling.
- Authors
Royer, P.-J.; Henrio, K.; Pain, M.; Loy, J.; Roux, A.; Tissot, A.; Lacoste, P.; Pison, C.; Brouard, S.; Magnan, A.; COLT consortium
- Abstract
<bold>Background: </bold>Airway epithelial cells (AEC) act as the first line of defence in case of lung infections. They constitute a physical barrier against pathogens and they participate in the initiation of the immune response. Yet, the modalities of pathogen recognition by AEC and the consequences on the epithelial barrier remain poorly documented.<bold>Method: </bold>We investigated the response of primary human AEC to viral (polyinosinic-polycytidylic acid, poly(I:C)) and bacterial (lipopolysaccharide, LPS) stimulations in combination with the lung remodeling factor Transforming Growth Factor-β (TGF-β).<bold>Results: </bold>We showed a strong production of pro-inflammatory cytokines (Interleukin (IL)-6, Tumor Necrosis Factor α, TNFα) or chemokines (CCL2, CCL3, CCL4, CXCL10, CXCL11) by AEC stimulated with poly(I:C). Cytokine and chemokine production, except CXCL10, was Toll Like Receptor (TLR)-3 dependent and although they express TLR4, we found no cytokine production after LPS stimulation. Poly(I:C), but not LPS, synergised with TGF-β for the production of matrix metalloproteinase-9 (MMP-9) and fibronectin. Mechanistic analyses suggest the secretion of Wnt ligands by AEC along with a degradation of the cellular junctions after poly(I:C) exposure, leading to the release of β-catenin from the cell membrane and stimulation of the Wnt/β-catenin pathway.<bold>Conclusion: </bold>Our results highlight the cross talk between TGF-β and TLR signaling in bronchial epithelium and its impact on the remodeling process.
- Subjects
EPITHELIAL cells; PATHOGENIC microorganisms; IMMUNE response; IMMUNOLOGY; ANERGY; CELL culture; CELL physiology; CELL receptors; CELLULAR signal transduction; CHEMOKINES; COMPARATIVE studies; CYTOKINES; CYTOSKELETAL proteins; GROWTH factors; RESEARCH methodology; MEDICAL cooperation; PROTEOLYTIC enzymes; RESEARCH; RESPIRATORY mucosa; EVALUATION research; LIPOPOLYSACCHARIDES
- Publication
Respiratory Research, 2017, Vol 18, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-017-0690-y