Anti-inflammatory role of Alpha-1-Antitrypsin – insights on the mechanisms involved
Alpha 1-antitrypsin (AAT), a major inhibitor of neutrophil elastase, is classified as an acute-phase protein. Recently a new aspect of AAT action has emerged, as AAT was found to exhibit various anti-inflammatory characteristics when used in cellular and animal models, and administrated in patients with severe inherited AAT deficiency. Our current data in vitro and in vivo show that AAT can either up-regulate or down-regulate endotoxin-induced cytokine/chemokine expression and release in a time-dependent manner. We believe that a short-term enhancement of the endotoxin-induced cell activation may be the key mechanism by which the function of AAT and several other acute phase proteins, such as alpha1-acid glycoprotein, is accomplished. We hypothesis that the diseases associated with inherited AAT deficiency may not be due to entirely inadequate inhibition of elastase by AAT, but also to the inadequate acute-phase response and inability to eliminate invading pathogens and to resolve the inflammation processes. Therefore, a deeper understanding of the mechanisms involved in the biological activities of AAT during an acute-phase response is of particular importance. Acute inflammatory reactions, in contrast to chronic inflammatory reactions, are usually self-limiting and resolve. An understanding of how AAT switches pro-inflammatory pathways to the anti-inflammatory pathways necessary for resolution of inflammation may eventually allow the better exploitation of endogenous AAT and, possibly, other acute phase proteins, for the treatment of chronic inflammatory diseases, including chronic obstructive pulmonary disease.
Curriculum Vitae of Devipriya Subramaniyam
Devipriya Subramaniyam is currently pursuing her doctoral degree at the Hannover Medical School in Germany. She has completed her Bachelors degree in Industrial Biotechnology in India in 2000, followed by a Master's degree in Microbiology in Singapore in 2003. From 2004-2009 Ms Subramaniyam has studied the role of alpha-1 antitrypsin in chronic obstructive pulmonary diseases at the University Hospital in Malmö, Sweden.
Ms Subramaniyam's research interests include immunological aspects of inflammatory diseases. In her eALTA project "Anti-inflammatory role of alpha-1 antitrypsin – insights on the mechanisms involved", she investigated how alpha-1 antitrypsin regulates the acute inflammatory response in a mouse model of LPS-induced acute lung inflammation and which signalling pathways are involved.
Medical School Hannover