l-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells

This study tested the hypothesis that l-arginine (Arg) may stimulate cell proliferation and prevent lipopolysaccharide (LPS)-induced death of intestinal cells. Intestinal porcine epithelial cells (IPEC-1) were cultured for 4 days in Arg-free Dulbecco’s modified Eagle’s-F12 Ham medium (DMEM-F12) containing 10, 100 or 350 μM Arg and 0 or 20 ng/ml LPS. Cell numbers, protein concentrations, protein synthesis and degradation, as well as mammalian target of rapamycin (mTOR) and Toll-like receptor 4 (TLR4) signaling pathways were determined. Without LPS, IPEC-1 cells exhibited time- and Arg-dependent growth curves. LPS treatment increased cell death and reduced protein concentrations in IPEC-1 cells. Addition of 100 and 350 μM Arg to culture medium dose-dependently attenuated LPS-induced cell death and reduction of protein concentrations, in comparison with the basal medium containing 10 μM Arg. Furthermore, supplementation of 100 and 350 μM Arg increased protein synthesis and reduced protein degradation in both control and LPS-treated IPEC-1 cells. Consistent with the data on cell growth and protein turnover, addition of 100 or 350 μM Arg to culture medium increased relative protein levels for phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase-1, while reducing the relative levels of TLR4 and phosphorylated levels of nuclear factor-κB in LPS-treated IPEC-1 cells. These results demonstrate a protective effect of Arg against LPS-induced enterocyte damage through mechanisms involving mTOR and TLR4 signaling pathways, as well as intracellular protein turnover

Cellular and molecular events in acute pancreatitis

Acute pancreatitis (AP) is a common disease in which the underlying mechanisms of the local initiating events in the pancreas, the systemic dissemination of the inflammatory response and the development of remote organ dysfunction have not been fully clarified. AP is still associated with substantial morbidity and mortality. Clinical therapeutic strategies for AP have so far been mainly directed at supportive critical care. After the initial injury to the pancreatic acinar cells, the inflammatory mediators released from the inflamed acini trigger activating cascades through immunocompetent cells, leading to the development of systemic inflammatory response syndrome and multiple organ dysfunction syndrome. These damaged, inflamed acinar cells interact with activated, immigrated immune cells and inflammatory mediators and therefore amplify the inflammatory response in AP. Of these immune cells, neutrophils, monocytes/macrophages and T lymphocytes play critical roles in the pathogenesis of AP. Substantial evidence exists demonstrating the importance of inflammatory mediators such as cytokines, chemokines and adhesion molecules in the initiation of the progression of AP. Inflammatory mediators in damaged, inflamed acinar cells and activated immunocompetent cells are closely regulated through cellular signalling pathways, e.g. those involving nuclear factor-κB, mitogen-activated protein kinase, reactive oxygen species and protein kinase C. Therefore, cellular and molecular events are crucial to the pathophysiological mechanisms underlying AP. Single- or multi-modal treatment regimens directed at regulating different steps in the signalling pathways could represent future modes of management