Proinflammatory effect of AbetaPP induced ST6GAL1 secretion from C2C12 myogenic cell line [C2C12 miyojenik hücre hattında AbetaPP tarafından indüklenen ST6GAL1 salgılanmasının proinflamatuar etkisi]

Objective: ST6 beta-galactosamide α-2,6-sialyltranferase 1 (ST6GAL1), the major α2,6sialyltransferase responsible for the broad synthesis of glycoproteins and glycolipids, is another physiological substrate of Beta site APP-cleaving enzyme 1 (BACE1) other than amyloidbeta precursor protein (AbetaPP). We have previously shown that AbetaPP overexpression in C2C12 mouse myoblast cell line increased the expression and secretion of ST6GAL1 enzyme under in vitro conditions. Since the secretion of ST6GAL1 is known to be enhanced during inflammation, we investigated whether AbetaPP induced ST6GAL1 secretion from C2C12 cells affected proinflammatory cytokine production by J774 mouse macrophage cell line. Methods: J774 macrophage cells were cultured with conditioned medium derived from either AbetaPP or ST6GAL1 overexpressing C2C12 cells and analyzed for proinflammatory cytokine (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) expression by quantitative realtime PCR (qRT-PCR). Also, culture supernatants were analyzed for IL-1β release by ELISA. Results: The results of our study demonstrated that secretion of ST6GAL1 enzyme from either AbetaPP or ST6GAL1 overexpressing C2C12 cells induces the expression of TNF-α, IL-1β, IL-6 and the secretion of IL-1β by J774 macrophages. Conclusion: In our study, results were obtained pointing that secreted ST6GAL1 might have a potential role in the inflammation process observed in the muscle tissue. Our results should be confirmed under in vivo system.