TNF-alpha upregulates macroautophagic processing of APP/beta-amyloid in a human rhabdomyosarcoma cell line

Abstract

Sporadic inclusion body myositis is a chronic progressive, inflammatory disorder of the skeletal muscle. No effective treatment is available for this debilitating condition and the complex disease pathology is far from being understood. The major hallmark of the pathomechanisms is the co-occurrence of inflammatory as well as degenerative cascades including aggregates consisting of beta-amyloid within skeletal muscle fibers. Macroautophagy, a homeostatic process that shuttles cytoplasmic constituents into endosomal and lysosomal compartments, has recently been shown to be upregulated via the proinflammatoty cytokine TNF-alpha in human skeletal muscle cells. In a human cell line from rhabdomyosarcoma as a model to study muscle cells, we here show that TNT-alpha-mediated upregulation of macroautophagy modulates APP and beta-amyloid load and can be blocked by inhibition of macroautophagy. Thus, macroautophagy may be a crucial mediator between inflammation and beta-amyloid-associated degeneration in skeletal muscle. (C) 2012 Elsevier B.V. All rights reserved.