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Mediators of Inflammation
Volume 2017, Article ID 1434872, 10 pages
Research Article

Chemokines (CCL3, CCL4, and CCL5) Inhibit ATP-Induced Release of IL-1β by Monocytic Cells

1Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Giessen, Germany
2Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Giessen, Germany
3George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT, USA
4Department of Biology, University of Utah, Salt Lake City, UT, USA
5Department of Psychiatry, University of Utah, Salt Lake City, UT, USA
6Excellence Cluster Cardiopulmonary System (ECCPS), German Center for Lung Research (DZL), Giessen, Germany

Correspondence should be addressed to Veronika Grau; ed.nesseig-inu.dem.urihc@uarg.akinorev

Received 20 January 2017; Revised 31 March 2017; Accepted 20 April 2017; Published 5 July 2017

Academic Editor: Paul Proost

Copyright © 2017 Anca-Laura Amati et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Chemokines and ATP are among the mediators of inflammatory sites that can enter the circulation via damaged blood vessels. The main function of chemokines is leukocyte mobilization, and ATP typically triggers inflammasome assembly. IL-1β, a potent inflammasome-dependent cytokine of innate immunity, is essential for pathogen defense. However, excessive IL-1β may cause life-threatening systemic inflammation. Here, we hypothesize that chemokines control ATP-dependent secretion of monocytic IL-1β. Lipopolysaccharide-primed human monocytic U937 cells were stimulated with the P2X7 agonist BzATP for 30 min to induce IL-1β release. CCL3, CCL4, and CCL5 dose dependently inhibited BzATP-stimulated release of IL-1β, whereas CXCL16 was ineffective. The effect of CCL3 was confirmed for primary mononuclear leukocytes. It was blunted after silencing CCR1 or calcium-independent phospholipase A2 (iPLA2) by siRNA and was sensitive to antagonists of nicotinic acetylcholine receptors containing subunits α7 and α9. U937 cells secreted small factors in response to CCL3 that mediated the inhibition of IL-1β release. We suggest that CCL chemokines inhibit ATP-induced release of IL-1β from U937 cells by a triple-membrane-passing mechanism involving CCR, iPLA2, release of small mediators, and nicotinic acetylcholine receptor subunits α7 and α9. We speculate that whenever chemokines and ATP enter the circulation concomitantly, systemic release of IL-1β is minimized.