Browse by author
Lookup NU author(s): Dr Mike Althaus
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1β release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing α9 and α10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of α9 subunits or heteromeric receptors containing α9 and α10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions.
Author(s): Richter K, Mathes V, Fronius M, Althaus M, Hecker G, Krasteva-Christ G, Padberg W, Hone AJ, McIntosh JM, Zakrzewicz A, Grau V
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Print publication date: 28/06/2016
Online publication date: 28/06/2016
Acceptance date: 06/06/2016
Date deposited: 22/11/2018
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
PubMed id: 27349288
Altmetrics provided by Altmetric