Characterization of synthetic lung surfactant activity against proinflammatory cytokines in human monocytes.
Our previous study demonstrated that the smallest synthetic peptide with the sequence CPVHLKRLLLLLLLLLLLLLLLL, 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-alpha (TNF-a), interleukin (IL)-8, IL-6, IL-1beta, and macrophage migration inhibitory factor (MIF) was reduced by lipopolysaccharide (LPS) in monocytes was examined. Levels of these cytokines were measured by enzyme-linked immunosorbent assay. It was found that SLS significantly and dose dependently inhibited the secretion of TNF-alpha 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 both anti inflammatory activity and surface activity.
Otsubo
Eiji
E
Research Center, Mitsubishi Pharma Corporation, Kisarazu, Chiba, Japan. Otsubo.Eiji@mc.m-pharma.co.jp
Irimajiri
Kiyohiro
K
Takei
Tsunetomo
T
Nomura
Masato
M
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000494:pharmacology*
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D003907:Dexamethasone