PMID- 29962852
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1226-4512 (Print)
IS  - 2093-3827 (Electronic)
IS  - 1226-4512 (Linking)
VI  - 22
IP  - 4
DP  - 2018 Jul
TI  - Adenine attenuates lipopolysaccharide-induced inflammatory reactions.
PG  - 379-389
LID - 10.4196/kjpp.2018.22.4.379 [doi]
AB  - 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-alpha and IL-6 and inflammatory lipid mediators, prostaglandin E(2) and 
      leukotriene B(4). Adenine impeded signaling pathways eliciting production of 
      these inflammatory mediators. It suppressed IkappaB phosphorylation, nuclear 
      translocation of nuclear factor kappaB (NF-kappaB), 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-alpha, IL-6 and IL-13 and also hindered phosphorylation of NF-kappaB and Akt. In 
      peritoneal cavity, adenine suppressed the LPS-induced production of TNF-alpha and 
      IL-6 by peritoneal cells in mice. These results show that adenine attenuates the 
      LPS-induced inflammatory reactions.
FAU - Silwal, Prashanta
AU  - Silwal P
AD  - Department of Medical Science, College of Medicine, Chungnam National University, 
      Daejeon 35015, Korea.
FAU - Lim, Kyu
AU  - Lim K
AD  - Department of Biochemistry, College of Medicine, Chungnam National University, 
      Daejeon 35015, Korea.
FAU - Heo, Jun-Young
AU  - Heo JY
AD  - Department of Biochemistry, College of Medicine, Chungnam National University, 
      Daejeon 35015, Korea.
FAU - Park, Jong Il
AU  - Park JI
AD  - Department of Biochemistry, College of Medicine, Chungnam National University, 
      Daejeon 35015, Korea.
FAU - Namgung, Uk
AU  - Namgung U
AD  - Department of Oriental Medicine, Daejeon University, Daejeon 34520, Korea.
FAU - Park, Seung-Kiel
AU  - Park SK
AD  - Department of Medical Science, College of Medicine, Chungnam National University, 
      Daejeon 35015, Korea.
AD  - Department of Biochemistry, College of Medicine, Chungnam National University, 
      Daejeon 35015, Korea.
LA  - eng
PT  - Journal Article
DEP - 20180625
PL  - Korea (South)
TA  - Korean J Physiol Pharmacol
JT  - The Korean journal of physiology & pharmacology : official journal of the Korean 
      Physiological Society and the Korean Society of Pharmacology
JID - 9709505
PMC - PMC6019877
OTO - NOTNLM
OT  - Adenine
OT  - Inflammation
OT  - Lipopolysaccharide
OT  - Macrophages
OT  - Mast cells
OT  - Toll-like receptor 4
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest.
EDAT- 2018/07/03 06:00
MHDA- 2018/07/03 06:01
PMCR- 2018/07/01
CRDT- 2018/07/03 06:00
PHST- 2017/09/29 00:00 [received]
PHST- 2018/02/18 00:00 [revised]
PHST- 2018/04/06 00:00 [accepted]
PHST- 2018/07/03 06:00 [entrez]
PHST- 2018/07/03 06:00 [pubmed]
PHST- 2018/07/03 06:01 [medline]
PHST- 2018/07/01 00:00 [pmc-release]
AID - 10.4196/kjpp.2018.22.4.379 [doi]
PST - ppublish
SO  - Korean J Physiol Pharmacol. 2018 Jul;22(4):379-389. doi: 
      10.4196/kjpp.2018.22.4.379. Epub 2018 Jun 25.