Characterization of Synthetic Lung Surfactant Activity against Proinflammatory Cytokines in Human Monocytes

概要

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Our previous study demonstrated that the smallest synthetic peptide with the sequence CPVHLKRLLLLL-LLLLLLLLLLL, SP-CL16(6-28), admixed with phospholipid (synthetic lung surfactant, SLS) showed strong surface activity. In this study, we attempted to develop a dual-type surfactant with both anti inflammatory and surface activities. SP-CL16(6-28) was first chemically synthesized and then purified for use by centrifugal partition chromatography. A mixture of SP-CL16(6-28) and phospholipid complex was tested for anti inflammatory activity using the human monocyte cell line THP-1. Whether the suppression of tumor necrosis factor-α (TNF-α), interleukin (IL)-8,IL-6,IL-1β, and macrophage migration inhibitory factor (MIF) was reduced by lipopolysaccharide (LPS) in monocytes was examined. Levels of these cytokines were measured by enzymelinked immunosorbent assay. It was found that SLS significantly and dose dependently inhibited the secretion of TNF-α by THP-1 cells following stimulation with LPS. Dipalmitoylphosphatidylcoline did not inhibit the release of cytokines. These findings suggest that SLS has anti inflammatory activity. Therefore it should be possible to develop a SLS with bothanti inflammatory activity and surface activity.
公益社団法人日本薬学会の論文
2002-03-01