99 0 It has been suggested that the suppression of LOX could

It has been suggested that the suppression of 5-LOX could promote apoptotic signaling pathways in cancers [6]. However, the role of 5-LOX in modulating apoptotic factors and neutrophil activation during ANP has not yet been evaluated. In this study, we aimed to evaluate the expression of 5-LOX in pancreatic tissues during ANP and investigate whether inhibition of 5-LOX with the treatment zileuton could repress ANP-induced neutrophils activation, promote apoptosis, and attenuate pancreatic tissue pathology in pancreatic tissues during ANP.
Methods
Results
Discussion Acute pancreatitis is one of the most common diseases in digestion system [1]. Acute pancreatitis has several exhibitions, though 70–80% of all cases result from either gallstones or severe consumption of alcohol [1]. In most cases, acute pancreatitis is manageable as the past decade has witnessed significant improvement in the understanding and clinical control of acute pancreatitis [2]. However, under some conditions, a severe form of human acute pancreatitis, named as ANP, can induce whole-body inflammation and death [4]. During ANP, the release of inflammatory factors and mediators results in the systemic inflammatory response syndrome [4]. As the disease persists, organ failure happens as the results of severe infection of pancreatic necrosis [4]. Recent studies showed that LTs are the essential mediators involved in the systemic inflammation and disease pathogenesis during ANP and 5-LOX is the rate-limiting enzyme for LTs metabolism [10]. It is suggested that inhibition of 5-LOX can repress the activation of LTs and attenuate inflammation effect [10]. Indeed, a previous study showed that treatment with zileuton, a specific inhibitor for 5-LOX, attenuated inflammatory factors in a rat model of focal cerebral ischemia presumably by repressing nuclear factor kappa b 99 0 (NFkB, 11). However, the role of 5-LOX in regulating inflammation reaction is still largely unknown. In this study, we show that zileuton downregulates mRNA and protein levels of 5-LOX, represses neutrophils activation, activates apoptotic factors, and attenuates pancreatic tissue pathology in the rat model of ANP, suggesting that those two pathways are associated with the protective role of inhibition of 5-LOX in pancreatic tissue pathology during ANP. Acute pancreatitis has long been recognized as an organ dysfunction of the pancreas [1]. However, accumulating evidence suggests that acute pancreatitis is a systemic effect of pancreatic disease. During disease pathology, a systemic inflammation is activated and organ failures are the critical event in acute pancreatitis [12]. Indeed, recent studies show that inflammatory mediators, such as chemokines, are produced during ANP and lead to tissue inflammatory reaction. If this inflammatory reaction persists, it can result in a systemic inflammatory response syndrome (SIRS) and activation of systemic leukocytes [12]. Up to date, a number of inflammatory mediators have been identified to be involved in the pathophysiology of acute pancreatitis: hydrogen sulfide (H2S), TNF-α, IL-1β, IL-6/8/10, ICAM-1, monocyte chemoattractant protein-1 (MCP-1), neutral endopeptidase (NEP), and platelet activating factor (PAF) [12]. Activation of neutrophils is suggested to participate in this inflammatory mediator releasing. When activated, neutrophils release protein proteases, metabolites, and inflammatory factors [13]. In addition, neutrophils could accumulate on the inflammatory sites of the tissue and recruit multiple inflammatory mediators such as IL-1, TNF, and PAF, which damages the integrity of blood capillaries and boosts the releasing of these inflammatory mediators into blood [13]. Moreover, activation of neutrophils upregulates protein levels of cell adhesion molecules [13]. Under the normal condition, cell adhesion molecules are expressed at a very low level. However, as the result of neutrophils activation, cell adhesion molecules are highly expressed, which prompts the adhesion of neutrophils onto the inflammatory sites [13]. Based on those facts, it is suggested that repression of the neutrophils activation can decrease the releasing of inflammatory mediators and attenuate tissue inflammatory reaction.