Abstract | AIMS: 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.
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Authors | Shizuka Hirai, Sho Horii, Yoshiaki Matsuzaki, Shin Ono, Yuki Shimmura, Kenji Sato, Yukari Egashira |
Journal | Life sciences
(Life Sci)
Vol. 117
Issue 1
Pg. 1-6
(Nov 04 2014)
ISSN: 1879-0631 [Electronic] Netherlands |
PMID | 25225121
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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