Article (Scientific journals)
An essential role of syntaxin 3 protein for granule exocytosis and secretion of IL-1α, IL-1β, IL-12b, and CCL4 from differentiated HL-60 cells
Naegelen, Isabelle; Plançon, Sébastien; Nicot, Nathalie et al.
2014In Journal of Leukocyte Biology, 97
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Keywords :
SNARE proteins; cytokines; extracellular release; gelatinase granules; neutrophils
Abstract :
[en] Besides their roles in the killing of pathogens, neutrophils have the capacity to package a variety of cytokines into cytoplasmic granules for subsequent release upon inflammatory conditions. Because the rapid secretion of cytokines orchestrates the action of other immune cells at the infection site and thus, can contribute to the development and chronicity of inflammatory diseases, we aimed to determine the intracellular SNARE machinery responsible for the regulation of cytokine secretion and degranulation. From a constructed gene-expression network, we first selected relevant cytokines for functional validation by the CBA approach. We established a cytokine-secretion profile for human neutrophils and dHL-60 cells, underlining their similar ability to secrete a broad variety of cytokines within proinflammatory conditions mimicked by LPS stimulation. Secondly, after screening of SNARE genes by microarray experiments, we selected STX3 for further functional studies. With the use of a siRNA strategy, we show that STX3 is clearly required for the maximal release of IL-1α, IL-1β, IL-12b, and CCL4 without alteration of other cytokine secretion in dHL-60 cells. In addition, we demonstrate that STX3 is involved in MMP-9 exocytosis from gelatinase granules, where STX3 is partly localized. Our results suggest that the secretion of IL-1α, IL-1β, IL-12b, and CCL4 occurs during gelatinase degranulation, a process controlled by STX3. In summary, these findings provide first evidence that STX3 has an essential role in trafficking pathways of cytokines in neutrophil granulocytes.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Naegelen, Isabelle ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit > Calcium Signaling and Inflammation
Plançon, Sébastien ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit > Calcium Signaling and Inflammation
Nicot, Nathalie;  Centre de Recherche Public Santé, Luxembourg
Kaoma, Tony;  Centre de Recherche Public Santé, Luxembourg
Muller, Arnaud;  Centre de Recherche Public Santé, Luxembourg
Vallar, Laurent;  Centre de Recherche Public Santé, Luxembourg
Tschirhart, Eric ;  University of Luxembourg > Central Administration
Bréchard, Sabrina ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit > Calcium Signaling and Inflammation
Language :
English
Title :
An essential role of syntaxin 3 protein for granule exocytosis and secretion of IL-1α, IL-1β, IL-12b, and CCL4 from differentiated HL-60 cells
Publication date :
29 December 2014
Journal title :
Journal of Leukocyte Biology
ISSN :
0741-5400
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
97
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 23 January 2015

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