Reference - Detail
|Author||Hirai S, Horii S, Matsuzaki Y, Ono S, Shimmura Y, Sato K, Egashira Y.|
|Title||Anti-inflammatory effect of pyroglutamyl-leucine on lipopolysaccharide-stimulated RAW 264.7 macrophages.|
AIMS:Food-derived peptides have been reported to yield a variety of health promoting activities. Pyroglutamyl peptides are contained in the wheat gluten hydrolysate. In the present study, we investigated the effect of pyroglutamyl dipeptides on the lipopolysaccharide (LPS)-induced inflammation in macrophages.
MAIN METHODS:RAW 264.7 macrophages were treated with LPS and various concentrations of pyroglutamyl-leucine (pyroGlu-Leu), -valine (pyroGlu-Val), -methionine (pyroGlu-Met), and -phenylalanine (pyroGlu-Phe). Cell viability/proliferation and various inflammatory parameters were measured by the established methods including ELISA and western blotting. The binding of fluorescein isothiocyanate-labeled LPS to RAW 264.7 cells was also measured fluorescently.
KEY FINDINGS:All the tested dipeptides significantly inhibited the secretion of nitric oxide, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 from LPS-stimulated RAW 264.7 macrophages. Above all, pyroGlu-Leu inhibited the secretion of all these inflammatory mediators even at the lowest dose (200μg/ml). PyroGlu-Leu dose-dependently suppressed IκBα degradation and MAPK (JNK, ERK, and p38) phosphorylation in LPS-stimulated RAW 264.7 cells. On the other hand, it did not affect the binding of LPS to the cell surface.
SIGNIFICANCE:Our results indicated that pyroGlu-Leu inhibits LPS-induced inflammatory response via the blocking of NF-κB and MAPK pathways in RAW 264.7 macrophages.
|MeSH||Animals Anti-Inflammatory Agents / administration & dosage Anti-Inflammatory Agents / pharmacology* Blotting, Western Cell Line Dipeptides / administration & dosage Dipeptides / pharmacology* Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Inflammation / drug therapy* Inflammation / pathology Inflammation Mediators / metabolism* Interleukin-6 / metabolism Lipopolysaccharides / toxicity MAP Kinase Signaling System / drug effects Macrophages / drug effects* Macrophages / pathology Mice NF-kappa B / metabolism Nitric Oxide / metabolism Phosphorylation / drug effects Pyrrolidonecarboxylic Acid / administration & dosage Pyrrolidonecarboxylic Acid / analogs & derivatives* Pyrrolidonecarboxylic Acid / pharmacology Tumor Necrosis Factor-alpha / metabolism|
|WOS Category||MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY|
|Human and Animal Cells|