Antimicrobial peptide P18 inhibits inflammatory responses by LPS- but not by IFN-gamma-stimulated macrophages.
Antimicrobial peptide P18 markedly inhibited the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, whereas magainin 2 did not inhibit these activities. P18 dose-dependently reduced nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophage cells, with complete inhibition at 20 microg P18 ml(-1). In contrast, P18 had no effect on NO production and the expression of iNOS mRNA and iNOS protein by interferon-gamma (IFN-gamma)-stimulated RAW264.7 cells, suggesting P18 selectively inhibits LPS-stimulated inflammatory responses in macrophages. An LAL assay showed that P18 has strong LPS-neutralizing activity, indicating that P18 inhibits the inflammatory responses in LPS-stimulated macrophages by direct binding to LPS. Collectively, our results indicate that P18 has promising therapeutic potential as a novel anti-inflammatory as well as antimicrobial agent.
Nan
Yong Hai
YH
Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju, 501-759, Republic of Korea.
Jeon
Young Jin
YJ
Park
Il-Seon
IS
Shin
Song Yub
SY
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000178:diet therapy / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D054806:Magainins; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D029867:Xenopus Proteins / Q000494:pharmacology
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D054806:Magainins; C447608:P18 antimicrobial peptide; D014409:Tumor Necrosis Factor-alpha; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse