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The ERGIC-resident SNARE Sec22b regulates nitric oxide and cytokine production in dendritic cells

Arango Duque, Guillermo; Dion, Renaud; Descoteaux, J.; Descoteaux, Albert . The ERGIC-resident SNARE Sec22b regulates nitric oxide and cytokine production in dendritic cells In: 16e symposium annuel de parasitologie moléculaire du Québec, 6-7 juin 2016, Université McGill, Montréal, QC.

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Résumé

Through a series of highly orchestrated membrane fusion events, LPS-activated phagocytes mount an effective inflammatory response through the secretion of effectors such as cytokines and nitric oxide (NO). Within the secretory pathway, the ER-Golgi intermediate compartment (ERGIC) plays a key role in the synthesis and secretion of these molecules to the extracellular milieu. Members of the soluble NSF attachment receptor (SNARE) family play a pivotal role in regulating vesicle trafficking among the various cell organelles. Sec22b, an ERGIC-resident SNARE that regulates protein trafficking from the endoplasmic reticulum (RE) to the Golgi, controls phagocytosis and antigen cross-presentation in myeloid cells. Nitric oxide (NO) is synthesized by the inducible nitric oxide synthase (iNOS) in the immune system, and its cellular localization regulates enzymatic activity, which in turn occurs partly at the Golgi. Whether the ERGIC and its associated SNAREs control iNOS production and activity, and cytokine secretion, is unknown. Using dendritic cells and macrophages, we demonstrated that Brefeldin A- and Monensin-mediated disruption of ER-Golgi transport hindered NO and cytokine release by downregulating iNOS and cytokine protein and mRNA levels. This prompted us to study the role of the SNARE Sec22b in this phenomenon. In LPS-stimulated JAWSII cells transduced with shRNA to Sec22b, we found that NO and cytokine release were abrogated. In Sec22b-KD cells, the expression of iNOS and cytokines was inhibited at the protein and mRNA levels. This correlated with decreased activation of the MAPK signalling pathway and reduced IκB degradation. We also found that Sec22b partly colocalizes with NFκB, which helps relay LPS-induced signals to the nucleus. We are currently testing the possibility that Sec22b may be directly mediating NFκB translocation to the nucleus. Collectively, our data unveil a novel function for the ERGIC-bound SNARE Sec22b in the production and release of inflammatory mediators.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Présentation par affiche
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 01 mai 2018 20:50
Dernière modification: 01 mai 2018 20:50
URI: http://espace.inrs.ca/id/eprint/7079

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