Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains
In addition to providing mechanical stability, growing evidence suggests that surfactant lipid components can modulate inflammatory responses in the lung. However, little is known of the molecular mechanisms involved in the immunomodulatory action of surfactant lipids. This study investigates the ef...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520305381 |
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| author | Wondwossen Abate Abdulaziz A. Alghaithy Joan Parton Kenneth P. Jones Simon K. Jackson |
| author_facet | Wondwossen Abate Abdulaziz A. Alghaithy Joan Parton Kenneth P. Jones Simon K. Jackson |
| author_sort | Wondwossen Abate |
| collection | DOAJ |
| description | In addition to providing mechanical stability, growing evidence suggests that surfactant lipid components can modulate inflammatory responses in the lung. However, little is known of the molecular mechanisms involved in the immunomodulatory action of surfactant lipids. This study investigates the effect of the lipid-rich surfactant preparations Survanta®, Curosurf®, and the major surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) on interleukin-8 (IL-8) gene and protein expression in human A549 lung epithelial cells using immunoassay and PCR techniques. To examine potential mechanisms of the surfactant lipid effects, Toll-like receptor 4 (TLR4) expression was analyzed by flow cytometry, and membrane lipid raft domains were separated by density gradient ultracentrifugation and analyzed by immunoblotting with anti-TLR4 antibody. The lipid-rich surfactant preparations Survanta®, Curosurf®, and DPPC, at physiological concentrations, significantly downregulated lipopolysaccharide (LPS)-induced IL-8 expression in A549 cells both at the mRNA and protein levels. The surfactant preparations did not affect the cell surface expression of TLR4 or the binding of LPS to the cells. However, LPS treatment induced translocation of TLR4 into membrane lipid raft microdomains, and this translocation was inhibited by incubation of the cells with the surfactant lipid. This study provides important mechanistic details of the immune-modulating action of pulmonary surfactant lipids. |
| first_indexed | 2024-12-16T12:45:14Z |
| format | Article |
| id | doaj.art-2b96afc670fc4e8a9aa8079cdedb5d09 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T12:45:14Z |
| publishDate | 2010-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-2b96afc670fc4e8a9aa8079cdedb5d092022-12-21T22:31:19ZengElsevierJournal of Lipid Research0022-22752010-02-01512334344Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domainsWondwossen Abate0Abdulaziz A. Alghaithy1Joan Parton2Kenneth P. Jones3Simon K. Jackson4Centre for Research in Biomedicine, Faculty of Health and Life Science, University of the West of England, Bristol, UKDepartment of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UKDepartment of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UKSchool of Applied Sciences, University of Wales Institute Cardiff, Cardiff, UKTo whom correspondence should be addressed; Centre for Research in Biomedicine, Faculty of Health and Life Science, University of the West of England, Bristol, UKIn addition to providing mechanical stability, growing evidence suggests that surfactant lipid components can modulate inflammatory responses in the lung. However, little is known of the molecular mechanisms involved in the immunomodulatory action of surfactant lipids. This study investigates the effect of the lipid-rich surfactant preparations Survanta®, Curosurf®, and the major surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) on interleukin-8 (IL-8) gene and protein expression in human A549 lung epithelial cells using immunoassay and PCR techniques. To examine potential mechanisms of the surfactant lipid effects, Toll-like receptor 4 (TLR4) expression was analyzed by flow cytometry, and membrane lipid raft domains were separated by density gradient ultracentrifugation and analyzed by immunoblotting with anti-TLR4 antibody. The lipid-rich surfactant preparations Survanta®, Curosurf®, and DPPC, at physiological concentrations, significantly downregulated lipopolysaccharide (LPS)-induced IL-8 expression in A549 cells both at the mRNA and protein levels. The surfactant preparations did not affect the cell surface expression of TLR4 or the binding of LPS to the cells. However, LPS treatment induced translocation of TLR4 into membrane lipid raft microdomains, and this translocation was inhibited by incubation of the cells with the surfactant lipid. This study provides important mechanistic details of the immune-modulating action of pulmonary surfactant lipids.http://www.sciencedirect.com/science/article/pii/S0022227520305381lipopolysaccharidecytokinesinflammation |
| spellingShingle | Wondwossen Abate Abdulaziz A. Alghaithy Joan Parton Kenneth P. Jones Simon K. Jackson Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains Journal of Lipid Research lipopolysaccharide cytokines inflammation |
| title | Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains |
| title_full | Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains |
| title_fullStr | Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains |
| title_full_unstemmed | Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains |
| title_short | Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains |
| title_sort | surfactant lipids regulate lps induced interleukin 8 production in a549 lung epithelial cells by inhibiting translocation of tlr4 into lipid raft domains |
| topic | lipopolysaccharide cytokines inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520305381 |
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