Regulatory Function of Cytokines Signaling in Idiopathic Inflammatory Myopathies

The complexity of intercellular interplay in inflammatory and autoimmune processes is mainly regulated by cytokines, chemokines and other soluble and membrane-bound mediators produced by a variety of cells. We established the isolation and cultivation of functional primary murine skeletal muscle cells and primary murine microvascular cells to characterize the regulatory function of cytokines signalling in idiopathic inflammatory myopathies, focusing on the effect on GM-CSF and its receptor. In order to achieve this, we stimulated the cells with TNF, IF and a combination of the two. These experiments demonstrated a functional expression of GM-CSF and its receptor in both cell types. The highest expression levels of GM-CSF were observed under treatment with TNF and TNF+IF by primary murine skeletal muscle cells. Under basal conditions, the cells showed no detectable GM-CSF expression. Interestingly, muscle cells expressed higher levels of GM-CSF receptor, while endothelial cells expressed higher levels of GM-CSF, also under basal conditions. The stimulation with IFN of primary murinemicrovascular endothelial cells led to a significant downregulation of GM-CSF receptor expression below detection limits.