Proinflammatory cell stress in sporadic inclusion body myositis muscle: overexpression of  B-crystallin is associated with amyloid precursor protein and accumulation of  -amyloid

Abstract

Our results suggest that alphaB-crystallin is associated with overexpression of APP in sIBM muscle and that upregulation of alphaB-crystallin precedes accumulation of beta-amyloid. The data help to better understand early pathological changes and underscore the fact that a network of cell stress, inflammation and degeneration is relevant to sIBM.

188th ENMC International Workshop: Inclusion Body Myositis, 2–4 December 2011, Naarden, The Netherlands

“…A similar relationship, possibly mediated by the GSK-3b kinase, has been demonstrated in an animal model of the disease [10]. Apart from inflammation, an early cell stress response around aB-crystallin and nitric oxide is present in IBM muscle and may precede accumulation of b-amyloid [9,11]. The cytokines IFN-c and IL-1b have been demonstrated to be key inducers of accumulation of b-amyloid in muscle cells.…”

Pathophysiology of inflammatory and autoimmune myopathies

“…It appears therefore that, aB-crystallin may be an early event associated with a stress-response that precedes accumulation of b-amyloid. This view was further supported by in vitro studies which demonstrated that accumulation of b-amyloid, upon pro-inflammatory cell-stress, was preceded by upregulation of APP and aB-crystallin [103]. The noted cross-talk between inflammation and degeneration, although does not provide any information on what is the primary event, argues that inflammation may enhance the protein misfolding process.…”

“…aB-crystallin had been immunolocalized to healthy-appearing muscle fibers in IBM muscle almost a decade ago [102]. In a current quantitative assessment of multi-labeling and serial immunohistochemistry, a positive correlation between aB-crystallin and bamyloid-associated markers was found in sIBM muscles [103]. The normal-appearing muscle fibers that were positive for aBcrystallin were often double-positive for APP, while APP/bamyloid co-localized with markers of cell-stress and regeneration/degeneration.…”

Of amyloid and inflammation: causes of chronic muscle disease

“…These muscle fibres have been referred to as "X fibres", since it was assumed that they carry a very early pathological change, which would become manifest over time in the form of changes in cell structure, such as vacuoles for example. In a recently published work, our group was able to shown that αB-crystalline und β-amyloid correlate significantly with one another [16]. In particular, so-called "X fibres" were often positive for APP or even β-amyloid, which could also be shown together with other markers for regeneration or degeneration, such as NCAM or desmin in the same fibre.…”