TY - JOUR
T1 - 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
AU - Naegelen, Isabelle
AU - Plançon, Sébastien
AU - Nicot, Nathalie
AU - Kaoma, Tony
AU - Muller, Arnaud
AU - Vallar, Laurent
AU - Tschirhart, Eric J.
AU - Bréchard, Sabrina
N1 - Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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-12β, 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.
AB - 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-12β, 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.
KW - Cytokines
KW - Extracellular release
KW - Gelatinase granules
KW - Neutrophils
KW - SNARE proteins
UR - http://www.scopus.com/inward/record.url?scp=84928759821&partnerID=8YFLogxK
U2 - 10.1189/jlb.3A0514-254RR
DO - 10.1189/jlb.3A0514-254RR
M3 - Article
C2 - 25548252
AN - SCOPUS:84928759821
SN - 0741-5400
VL - 97
SP - 557
EP - 571
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -