Summary of Effects of APPA on Neutrophils

AKLRD, in collaboration with the University of Liverpool, were accepted for a presentation at the 2016 OARSI (Osteoarthritis Research Society International) Congress

Summary of Effects of APPA on Human Neutrophils Function

APPA is a synergistic combination of 2 synthetic anti-inflammatory molecules. APPA has shown efficacy in several animal models of osteoarthritis, decreasing pain and meniscal cartilage damage. Its efficacy is thought to be due to the effects of the constituent components on various levels of regulation of the transcription factor, NF-κB but as we show here also has effects upon other signalling pathways and neutrophil processes.

Neutrophils are the first line of defence against invading pathogens and are vital to fight infection. Their function in vivo and in vitro is regulated by the activities of a number of cytokines. These cells are potent producers of reactive oxidants species (ROS, activators of NF-κB) via an NADPH oxidase and many inflammatory functions are also regulated by NF-κB activation.

Summary:

  • APPA did not interfere with vital neutrophil functions such as bacteria killing and the processes that aid this, such as prolonged lifespan, migration and phagocytosis
  • APPA is a strong scavenger of reactive oxygen species and also appears to up regulate NRF2, an anti-inflammatory regulator of antioxidant proteins
  • APPA inhibited the production of neutrophil extracellular traps (NETs)
  • APPA decreased degranulation of neutrophils
  • APPA affected several signal transduction pathways both at the gene and protein levels

It is clear that APPA  via its two components, acts in an anti-inflammatory manner without affecting host defence mechanisms involved in bacterial killing. This work supports previous work observed here and in other laboratories on cell and animal models.

For more in depth information please see http://www.oarsijournal.com/article/S1063-4584(16)00620-8/abstract