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Anti-inflammatory effect of pyroglutamyl-leucine on lipopolysaccharide-stimulated RAW 264.7 macrophages.

AbstractAIMS:
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.
AuthorsShizuka Hirai, Sho Horii, Yoshiaki Matsuzaki, Shin Ono, Yuki Shimmura, Kenji Sato, Yukari Egashira
JournalLife sciences (Life Sci) Vol. 117 Issue 1 Pg. 1-6 (Nov 04 2014) ISSN: 1879-0631 [Electronic] Netherlands
PMID25225121 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Dipeptides
  • Inflammation Mediators
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • pyroglutamylleucine
  • Nitric Oxide
  • Pyrrolidonecarboxylic Acid
Topics
  • Animals
  • Anti-Inflammatory Agents (administration & dosage, pharmacology)
  • Blotting, Western
  • Cell Line
  • Dipeptides (administration & dosage, pharmacology)
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Inflammation (drug therapy, pathology)
  • Inflammation Mediators (metabolism)
  • Interleukin-6 (metabolism)
  • Lipopolysaccharides (toxicity)
  • MAP Kinase Signaling System (drug effects)
  • Macrophages (drug effects, pathology)
  • Mice
  • NF-kappa B (metabolism)
  • Nitric Oxide (metabolism)
  • Phosphorylation (drug effects)
  • Pyrrolidonecarboxylic Acid (administration & dosage, analogs & derivatives, pharmacology)
  • Tumor Necrosis Factor-alpha (metabolism)

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