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Journal of Lipid Research, Vol. 51, 334-344, February 2010
Copyright © 2010 by American Society for Biochemistry and Molecular Biology

Surfactant lipids regulate LPS-induced interleukin-8 production in A549 lung epithelial cells by inhibiting translocation of TLR4 into lipid raft domains

Wondwossen Abate^*, Abdulaziz A. Alghaithy, Joan Parton, Kenneth P. Jones and Simon K. Jackson^1,*

^* Centre for Research in Biomedicine, Faculty of Health and Life Science, University of the West of England, Bristol, UK
Department of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK
School of Applied Sciences, University of Wales Institute Cardiff, Cardiff, UK

¹ To whom correspondence should be addressed. e-mail: simon.jackson{at}uwe.ac.uk

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.

Supplementary key words lipopolysaccharide • cytokines • inflammation

Abbreviations: DPPC, dipalmitoyl phosphatidylcholine; IL-8, interleukin-8; LPS, lipopolysaccharide; mfi, mean fluorescence index; PC, phosphatidylcholine; SP, surfactant protein; TLR4, Toll-like receptor 4; TNF-, tumor necrosis factor-

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