Blockade of store-operated calcium entry reduces IL-17/TNF cytokine-induced Inflammatory response in human myoblasts - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue Frontiers in Immunology Année : 2019

Blockade of store-operated calcium entry reduces IL-17/TNF cytokine-induced Inflammatory response in human myoblasts

Résumé

Muscle inflammation as in idiopathic inflammatory myopathies (IIM) leads to muscle weakness, mononuclear cell infiltration, and myofiber dysfunction affecting calcium channels. The effects of interleukin-17A (IL-17) and tumor necrosis factor-alpha (TNF alpha) on inflammation and calcium changes were investigated in human myoblasts. Human myoblasts were exposed to IL-17 and/or TNF alpha with/without store-operated Ca2+ entry (SOCE) inhibitors (2-ABP or BTP2). For co-cultures, peripheral blood mononuclear cells (PBMC) from healthy donors activated or not with phytohemagglutinin (PHA) were added to myoblasts at a 5:1 ratio. IL-17 and TNF alpha induced in synergy CCL20 and IL-6 production by myoblasts (> 14-fold). PBMC-myoblast co-cultures enhanced CCL20 and IL-6 production in the presence or not of PHA compared to PBMC or myoblast monocultures. Anti-IL-17 and/or anti-TNF alpha decreased the production of IL-6 in co-cultures (p < 0.05). Transwell system that prevents direct cell-cell contact reduced CCL20 (p < 0.01) but not IL-6 secretion. IL-17 and/or TNF alpha increased the level of the ER stress marker Grp78, mitochondrial ROS and promoted SOCE activation by 2-fold (p < 0.01) in isolated myoblasts. SOCE inhibitors reduced the IL-6 production induced by IL-17/TNF alpha. Therefore, muscle inflammation induced by IL-17 and/or TNF alpha may increase muscle cell dysfunction, which, in turn, increased inflammation. Such close interplay between immune and non-immune mechanisms may drive and increase muscle inflammation and weakness.
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hal-02619749 , version 1 (25-05-2020)

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Audrey Beringer, Yves Gouriou, Fabien Lavocat, Michel Ovize, Pierre Miossec. Blockade of store-operated calcium entry reduces IL-17/TNF cytokine-induced Inflammatory response in human myoblasts. Frontiers in Immunology, 2019, 9, ⟨10.3389/fimmu.2018.03170⟩. ⟨hal-02619749⟩
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