Abstract |
Reduced scytonemin (R-scy) and scytonemin (Scy) isolated from Nostoc commune exhibit anti- tumor and ultraviolet-absorbing properties. In this study, we examined the effects of R-scy and Scy on the induction of nitric oxide (NO) production by lipopolysaccharide (LPS) and interferon-γ (IFNγ) in murine macrophage RAW264 cells. While both R-scy and Scy suppressed LPS/IFNγ-induced NO production, R-scy exhibited a stronger inhibitory effect compared with Scy. To further elucidate the mechanisms underlying the anti-inflammatory effects of R-scy, we examined the changes in the intracellular signaling cascade after LPS/IFNγ stimulation in cells. In addition to the attenuation of LPS/IFNγ-induced upregulation of the inducible isoform of NO synthase, R-scy decreased the activity of nuclear factor-κB, phosphatidylinositol 3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) after LPS/IFNγ stimulation. R-scy treatment increased heme oxygenase-1 (HO-1) expression by increasing the intracellular levels of reactive oxygen species and thereby activating nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element signaling. The induction of HO-1 by R-scy was inhibited by pretreatment with an antioxidant, N-acetyl- cysteine (NAC), as well as SB203580 and LY294002, inhibitors for p38 MAPK and PI3K/Akt, respectively. Our findings suggest that the anti-inflammatory effects of R-scy could involve both the ROS/PI3K/Akt and the p38 MAPK/Nrf2 signaling pathways.
|
Authors | Tomohiro Itoh, Mamoru Koketsu, Naoto Yokota, Shota Touho, Masashi Ando, Yasuyuki Tsukamasa |
Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
(Food Chem Toxicol)
Vol. 69
Pg. 330-8
(Jul 2014)
ISSN: 1873-6351 [Electronic] England |
PMID | 24795232
(Publication Type: Journal Article)
|
Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Adaptor Proteins, Signal Transducing
- Cytoskeletal Proteins
- Indoles
- Keap1 protein, mouse
- Kelch-Like ECH-Associated Protein 1
- Lipopolysaccharides
- NF-E2-Related Factor 2
- Nfe2l2 protein, mouse
- Phenols
- Reactive Oxygen Species
- scytonemin
- Nitric Oxide
- Interferon-gamma
- Heme Oxygenase-1
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
|
Topics |
- Adaptor Proteins, Signal Transducing
(metabolism)
- Animals
- Antioxidant Response Elements
(drug effects)
- Cell Line
(drug effects)
- Cytoskeletal Proteins
(metabolism)
- Heme Oxygenase-1
(metabolism)
- Indoles
(isolation & purification, pharmacology)
- Interferon-gamma
(metabolism, pharmacology)
- Kelch-Like ECH-Associated Protein 1
- Lipopolysaccharides
(pharmacology)
- Macrophages
(drug effects, metabolism)
- Mice
- NF-E2-Related Factor 2
(metabolism)
- Nitric Oxide
(metabolism)
- Nostoc commune
(chemistry)
- Phenols
(isolation & purification, pharmacology)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Reactive Oxygen Species
(metabolism)
- Signal Transduction
(drug effects)
|