N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibits tumour necrosis factor-alpha (TNF-alpha) production on lipopolysaccharide (LPS)-stimulated human neutrophils.
During gram-negative infections bacterial components, such as LPS and formylated peptides, exert profound physiological effects on polymorphonuclear neutrophils (PMN) resulting in increased neutrophil effector activities, including the generation of oxidative metabolites, degranulation, phagocytosis and cytokine release. There is not enough evidence about the relationships between LPS and formylated bacterial peptides in the triggering and regulation of the immune inflammatory response. In this study, we present evidence indicating that pretreatment of human PMN with a prototype formylated peptide such as fMLP results in the inhibition of TNF-alpha secretion, a key molecule that plays a central role in the pathogenesis of septic shock. This inhibitory effect of fMLP does not appear to alter the expression of LPS receptors or the transcriptional pathway of the TNF-alpha mRNA, but instead, fMLP reduces the expression of the membrane form of TNF-alpha on the PMN surface. These findings indicate that fMLP, a typical proinflammatory agent, could play, at least in determined conditions, an anti-inflammatory role.
Vulcano
M
M
División Immunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Alves Rosa
M F
MF
Minnucci
F S
FS
Cherñavsky
A C
AC
Isturiz
M A
MA
D015536:Down-Regulation / Q000187:drug effects; D006090:Gram-Negative Bacteria; D006801:Humans; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine