Reduced scytonemin isolated from Nostoc commune suppresses LPS/IFNγ-induced NO production in murine macrophage RAW264 cells by inducing hemeoxygenase-1 expression via the Nrf2/ARE pathway.

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)