Adenine attenuates lipopolysaccharide-induced inflammatory reactions.
10.4196/kjpp.2018.22.4.379
- Author:
Prashanta SILWAL
1
;
Kyu LIM
;
Jun Young HEO
;
Jong IL PARK
;
Uk NAMGUNG
;
Seung Kiel PARK
Author Information
1. Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. parksk@cnu.ac.kr
- Publication Type:Original Article
- Keywords:
Adenine;
Inflammation;
Lipopolysaccharide;
Macrophages;
Mast cells;
Toll-like receptor 4
- MeSH:
Adenine Nucleotides;
Adenine*;
Animals;
Bone Marrow;
Cell Line;
Cell Wall;
Colitis;
Cytokines;
Dextrans;
Gram-Negative Bacteria;
Hypersensitivity;
Inflammation;
Interleukin-13;
Interleukin-6;
Lymphocytes;
Macrophages;
Mammals;
Mast Cells;
Mice;
Mitogen-Activated Protein Kinases;
Nucleic Acids;
Peritoneal Cavity;
Phosphorylation;
Protein Kinases;
Sodium;
Toll-Like Receptor 4
- From:The Korean Journal of Physiology and Pharmacology
2018;22(4):379-389
- CountryRepublic of Korea
- Language:English
-
Abstract:
A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines TNF-α and IL-6 and inflammatory lipid mediators, prostaglandin E₂ and leukotriene B₄. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed IκB phosphorylation, nuclear translocation of nuclear factor κB (NF-κB), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of TNF-α, IL-6 and IL-13 and also hindered phosphorylation of NF-κB and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of TNF-α and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.
