LPS inhibits caspase 3-dependent apoptosis in RAW264.7 macrophages induced by the AMPK activator AICAR

AMP-activated kinase is a cellular energy sensor which is activated in stages of increased ATP consumption. Its activation has been associated with a number of beneficial effects such as decreasing inflammatory processes and the disease progress of diabetes and obesity, respectively. Furthermore, AMPK activation has been linked with induction of cell cycle arrest and apoptosis in cancer and vascular cells, indicating that it might have a therapeutic impact for the treatment of cancer and atherosclerosis. However, the impact of AMPK on the proliferation of macrophages, which also play a key role in the formation of atherosclerotic plaques and in inflammatory processes, has not been focused so far. We have assessed the influence of AICAR- and metformin-induced AMPK activation on cell viability of macrophages with and without inflammatory stimulation, respectively. In cells without inflammatory stimulation, we found a strong induction of caspase 3-dependent apoptosis associated with decreased mTOR levels and increased expression of p21. Interestingly, these effects could be inhibited by co-stimulation with bacterial lipopolysaccharide (LPS) but not by other proinflammatory cytokines suggesting that AICAR induces apoptosis via AMPK in a TLR4-pathway dependent manner.     

Titanium serum levels may remain elevated despite hip revision surgery for wear-through of an acetabular component.

A 62-year-old female patient showed radiographic signs of severe linear wear of the acetabular component six years after cementless total hip arthroplasty. This suggested wear-through of the acetabular liner with secondary wear of the titanium shell. At revision surgery wear-through of both the inlay and the acetabular shell were confirmed. Despite meticulous debridement serum titanium levels remained elevated for more than 12 months. Wear-through of a polyethylene acetabular liner with secondary wear of the titanium shell can lead to increased titanium serum levels. Titanium serum levels can remain highly elevated despite revision surgery.