Inflammatory role of the acinar cells during acute pancreatitis

Abstract

Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and finally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the final balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the first inflammatory signals which can mediate the activation and recruitment of circulating inflammatory cells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.

Keywords: Acinar cells; Acute pancreatitis; Inflammatory mediators; Signal pathways.

Figure 1

Signal transduction pathways involved in the expression of inflammatory mediators in pancreatic acinar cells. Abbreviations: ROS: Reactive oxygen species; PTPs: Proteine tyrosine phosphatases; TNF-α: Tumor necrosis factor-α; CCK-8: Cholecystokinin-8; PAAF: Pancreatitis-associated ascitic fluid; PKC: Protein kinase C; PKD: Protein kinase D; MKKKs: Mitogen activated protein kinase kinase kinases; MKKs: Mitogen activated protein kinase kinases; MAPKs: Mitogen activated protein kinases; MKPs: Mitogen kinase phosphatases; IKKs: ΙκB kinases; JNK: Jun N-terminal kinase; ERK: Extracellular-regulated kinase; JAKs: Janus kinases; NF-κB: Nuclear factor-κB; AP-1: Activating factor-1; STAT: Signal transducers and activators of transcription. Arrows: Activation; Dotted arrows: Inhibition.