Ultrashort Cationic Lipopeptides and Lipopeptoids Selectively Induce Cytokine Production in MacrophagesReport as inadecuate




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A series of ultrashort lipopeptides and lipopeptoids were tested for their ability to induce cytokine production in macrophages. Fourteen compounds were found to strongly induce production of chemokines Groα and IL-8, with a structural bias that was absent from previous antibacterial activity investigations. Compounds based on LysGlyLys and NLysGlyNLys sequences did not induce cytokine production, whereas those based on LysLysLys and NLysNLysNLys were active only when linked to a lipid tail at least sixteen carbons long. Three lipopeptides induced high levels of IL-8 production, above that of equivalent concentrations of cathelicidin LL-37, while no compound induced production of the pro-inflammatory cytokine TNF-α at or below 100 µM. Two compounds, peptoids C16OH-NLysNLysNLys and C16OH-NHarNHarNHar, were selective for IL-8 production and did not induce TNF-α or IL-1β. These compounds may prove beneficial for in vivo treatment of infectious disease, with improved bioavailability over LL-37 due to their protease-resistant scaffold.



Author: Brandon Findlay, Neeloffer Mookherjee , Frank Schweizer

Source: http://plos.srce.hr/



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