Mechanisms of the action of adenine on anti‐allergic effects in mast cells

• Published in: Immunity, Inflammation and Disease Inflammation and Disease, 2018-03, Vol.6 (1), p.97-105
• Main Authors: Hosoi, Toru, Ino, Shinsuke, Ohnishi, Fumie, Todoroki, Kenichi, Yoshii, Michiko, Kakimoto, Mai, Müller, Christa E., Ozawa, Koichiro
• Format: Article
• Language: English
• Subjects: adenine; Adenine - pharmacology; Adenosine; allergy; Animals; Antigens; Calcium Signaling - drug effects; Calcium Signaling - immunology; Cytokines; Histamine; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Hypersensitivity - pathology; Kinases; Laboratory animals; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - immunology; mast cells; Mast Cells - immunology; Mast Cells - pathology; Membranes; Mice; Oncogene Protein v-akt - immunology; Original Research; Phosphorylation; Proteins; Rats; Signal transduction; Syk Kinase - immunology
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.200

Introduction Mast cells play an important role in allergic responses. Methods We herein demonstrated the mechanisms of inhibitory effect of adenine on IgE/antigen‐induced degranulation and TNF‐α release in mast cells. Results We found that these effects were dependent on the amino group of adenine because purine only weakly inhibited degranulation. Adenine also inhibited Ca2+ ionophore‐ and thapsigargin‐induced degranulation, however, this inhibitory effect was weaker than that of the antigen. Therefore, the inhibitory effects of adenine on degranulation may be mediated before as well as after the Ca2+ raise under the antigen stimulus. Adenine inhibited antigen‐induced Syk and the subsequent induction of AKT and ERK activation under FcϵRI‐mediated signal. Adenine also attenuated antigen‐induced increase in Ca2+. Furthermore, adenine inhibited IgE/antigen‐induced IKKα/β activation, which is involved in degranulation. Finally, adenine protected mice against anaphylactic allergic responses in vivo. Conclusions The present study revealed a key role of adenine in the attenuation of allergic responses through the inhibition of Syk‐mediated signal transduction and IKK‐mediated degranulation. We demonstrated the amino group of adenine may play a key role in IgE/antigen‐induced degranulation in mast cells. The inhibitory effects of adenine on degranulation may be mediated before as well as after the Ca2+ raise under the antigen stimulus. We also provided key role of adenine in the attenuation of allergic responses through the inhibition of Syk‐mediated signal transduction and IKK‐mediated degranulation.