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Ramaline inhibits LPS‐induced NO release in macrophages by regulating MAPK and NF‐κB activities.
Author(s) -
Park HyeJin,
Yim Joung Han,
Pyo Suhkneung
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.966.6
Subject(s) - tlr4 , western blot , mapk/erk pathway , p38 mitogen activated protein kinases , lipopolysaccharide , nf κb , nitric oxide synthase , signal transduction , microbiology and biotechnology , innate immune system , macrophage , nitric oxide , chemistry , phosphorylation , biology , immune system , immunology , biochemistry , in vitro , gene , organic chemistry
Lipopolysaccharide (LPS) induces innate immune responses through TLR4 signaling and activated macrophages produce various inflammatory mediators including Nitric oxide (NO). NO produced by inducible NO synthase (iNOS) mediates a number of pathophysiological processes. Therefore, inhibiting NO production in macrophages is a potential therapeutic target in inflammatory diseases. Herein, we demonstrate that ramalin, a newly discovered antioxidant that is extracted from polar lichen, inhibits production of inflammatory mediators in macrophage‐like Raw 264.7 cell line. RT‐PCR and Western blot analysis demonstrated that ramalin suppressed the level of NO release through down‐regulating both mRNA and protein levels of iNOS. Western blot analysis also revealed that ramalin abrogated LPS‐induced phosphorylation of ERK, p38, and JNK as well as the expression of p65. Attenuated activity of NF‐κB by ramalin was also confirmed by Luciferase promoter assay. In addition, not only the surface level of LPS‐induced TLR4 but also its mRNA and protein levels were decreased by ramalin. Together, these results suggest that ramalin reduces NO release in macrophage through down‐regulation of TLR4 signaling which in turn suppresses MAPK and NF‐κB activities, and it would be a possible therapeutic approach to the treatment of inflammatory diseases.