Dual role for proteases in inflammation

Proteases identified in the lung were initially thought to be involved in extracellular matrix destruction. Today, several sources of evidence suggest that proteases have a multitude of regulatory functions in local inflammation processes, innate immunity, and infections. In particular enzymes belonging to serine and metallo proteases can modulate many biological functions by promoting chemokine and cytokine activation and degradation, cytokine receptor shedding, proteolysis of cytokine binding proteins and the activation of different specific cell surface receptors. Inflammatory processes are essential in host defense, but when excessive they can contribute to tissue injury, organ dysfunction, and lung diseases. Individual proteases can be both beneficial and/or detrimental in inflammatory reactions. However, the positive or negative contribution of a certain enzyme may depend on biological context such as location, substrate availability, inhibitors, cell type, and disease state. This review summarizes the current knowledge on the implication of proteases in the inflammation process and focuses on the dual role of certain proteases in both pro- and anti-inflammatory pathways. Further exploration and understanding of protease functions in lung inflammation will have important implications in health care and disease management.