Transfection of 12/15-lipoxygenase effectively alleviates inflammatory responses during experimental acute pancreatitis.

Abstract

Background: Acute pancreatitis (AP), the initially triggered inflammatory process in the pancreas, can be life-threatening. It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular components, maintain intracellular homeostasis, and promote apoptosis by upregulating the activity of caspases. Despite an increased understanding of the lipoxygenase pathway in inflammation and immune diseases, the role of the Alox15 gene product in modulating the inflammatory changes during AP is not well defined.

Aim: To investigate the effect of Alox15 expression in cerulein-induced AP in rats.

Methods: Model rats were transfected with Alox15 by injecting a recombinant lentivirus vector encoding Alox15 into the left gastric artery before inducing AP. The expression of Alox15 was then assessed at the mRNA and protein levels.

Results: Our in vivo results showed that serum amylase activity and pancreatic tissue water content were significantly reduced in Alox15-transfected rats. Further, the mRNA expression levels of tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1, as well as the protein expression of nuclear factor kappa B in pancreatic tissue were reduced. Additionally, we observed an upregulation of cleaved caspase-3 that implies an induction of apoptosis in pancreatic cells. The transfection of Alox15 resulted in a lower number of autophagic vacuoles in AP.

Conclusion: Our findings demonstrate a regulatory role of Alox15 in apoptosis and autophagy, making it a potential therapeutic target for AP.