Journalartikel

Jahr der Veröffentlichung: 2017

Zeitschrift: Mediators of Inflammation

Bandnummer: 2017

ISSN: 0962-9351

eISSN: 1466-1861

Open Access Status: Gold

DOI Link: https://doi.org/10.1155/2017/1434872

Verlag: Wiley

Abstract: 
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-1 beta,a potent inflammasome-dependent cytokine of innate immunity, is essential for pathogen defense. However, excessive IL-1 beta may cause life-threatening systemic inflammation. Here, we hypothesize that chemokines control ATP-dependent secretion of monocytic IL-1 beta. Lipopolysaccharide-primed human monocytic U937 cells were stimulated with the P2X7 agonist BzATP for 30 min to induce IL-1 beta release. CCL3, CCL4, and CCL5 dose dependently inhibited BzATP-stimulated release of IL-1 beta, 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 alpha 7 and alpha 9. U937 cells secreted small factors in response to CCL3 that mediated the inhibition of IL-1 beta release. We suggest that CCL chemokines inhibit ATP-induced release of IL-1 beta from U937 cells by a triple-membrane-passing mechanism involving CCR, iPLA2, release of small mediators, and nicotinic acetylcholine receptor subunits alpha 7 and alpha 9. We speculate that whenever chemokines and ATP enter the circulation concomitantly, systemic release of IL-1 beta is minimized.

Harvard-Zitierstil: Amati, A., Zakrzewicz, A., Siebers, K., Wilker, S., Heldmann, S., Zakrzewicz, D., et al. (2017) Chemokines (CCL3, CCL4, and CCL5) Inhibit ATP-Induced Release of IL-1β by Monocytic Cells, Mediators of Inflammation, 2017, Article 1434872. https://doi.org/10.1155/2017/1434872

APA-Zitierstil: Amati, A., Zakrzewicz, A., Siebers, K., Wilker, S., Heldmann, S., Zakrzewicz, D., Hecker, A., McIntosh, J., Padberg, W., & Grau, V. (2017). Chemokines (CCL3, CCL4, and CCL5) Inhibit ATP-Induced Release of IL-1β by Monocytic Cells. Mediators of Inflammation. 2017, Article 1434872. https://doi.org/10.1155/2017/1434872