Study Assess Prolyl Oligopeptidase Role in Acute Lung Injury

New study was done to assess the beneficial outcomes of Prolyl Oligopeptidase (POP)-inhibition in lung disease.

New study helps to estimate the effects of Prolyl Oligopeptidase (POP) inhibition mediated by KYP-2047 treatment in the pathophysiology of Acute Lung Injury (ALI) following II/R. KYP-2047 treatment reduced histological alteration in ileum and lung, reduced collagen amount and lowered inflammatory protein levels.

Intestinal ischemia-reperfusion develops when the blood flow to the intestines decreases, followed by the reestablishment of the blood supply to the ischemic tissue, resulting in intestinal mucosal barrier dysfunction, with consequent severe local and systemic inflammation. The study is published in Oncotarget.

‘KYP-2047, which acts through the activation of caspase enzymes, reduces apoptosis and enhances preservation of the lung after II/R injury.’
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Dr. Irene Paterniti from The University of Messina said, "Ischemic process causes a lack of oxygen supply and nutrients and the following restoration of blood circulation, called reperfusion, results in oxidative tissue damage and invasion of inflammatory mediators to neighboring organs."

II/R damage takes over when the decrease of blood flow in the intestine is followed by the restoration of blood required to the ischemic area, resulting in severe local and systemic inflammation which spreads to nearby organs.

Acute lung injury is the most serious complication after intestinal I/R. ALI is characterized by widespread organ inflammation with an acute onset and, although several pathophysiologic mechanisms of ALI in II/R have been partially proposed, the basic concepts remain mostly vague.

II/R provokes an important inflammatory response in nearby lung tissues, evidenced by neutrophilic infiltration, amplified myeloperoxidase levels and prominent vascular permeability in the lungs.

POP itself plays a role in supporting neutrophilic inflammation and this aspect involves POP to the pathology of various lung diseases.

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As the POP’s involvement in angiogenesis and inflammation has been highlighted, POP inhibitors have been developed and, between these, 4-phenyl-butanoyl-l-prolyl-2-cyanopyrrolidine appears to be the most powerful and extensively studied both in in vitro and in vivo models of inflammatory diseases.

So, the aim of the present study was to assess the beneficial outcomes of POP-inhibition in lung disease induced by an experimental mouse model of intestinal ischemia performed by SAO shock-mediated injury.

The Paterniti Research Team concluded in their Oncotarget Research Output that they proved this apoptosis modulation also in lung following II/R, highlighting that KYP-2047 treatment acting through the activation of caspase enzymes and thus reducing apoptosis, may enhance preservation of the lung after II/R injury.

Source-Medindia