Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe acute pancreatitis.

Exley, Andrew; Leese, T; Holliday, Mark; Swann, R. A.; Cohen, Jonathan

doi:10.1136/gut.33.8.1126

Cited by 186 publications

(79 citation statements)

References 24 publications

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“…S1A). Serum levels of TNF, a main causal factor of sepsis and endotoxemia (10)(11)(12)(13)(14)(15), had the peak at 1 h after LPS treatment to the same levels in WT and Rag2 −/− mice (Fig. S1A).…”

Section: T Cells Have a Protective Role In Lps Endotoxemia By Down-mentioning

confidence: 96%

T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation

Inoue¹,

Arikawa²,

Chen³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Endotoxemia is caused by excessive inflammation, but the immune system has various mechanisms to avoid collateral organ damage in endotoxemia. A handful of reports have shown that innate immune responses are suppressed by the adaptive immune system. However, the molecular mechanism by which adaptive immune cells suppress innate inflammatory responses is not clear. Here, we report that T cells are shown to interact with macrophages at the early stage of enodotoxemia and to prolong survival of mice through controlling TNF and IL-10 levels by macrophage CD40 stimulation. The cross-talk between CD40 and toll-like receptor (TLR4) signaling first mediates IL-1 receptor-associated kinase 1 (IRAK1) nuclear translocation and its binding to the IL-10 gene promoter in macrophages, without interfering with the NFκB pathway. IL-10 is then detected by macrophages in an autocrine fashion to destabilize Tnfa mRNA. To induce IRAK1-mediated IL-10 expression, signals from both CD40 and TLR4 are essential. CD40 signaling induces IRAK1 sumoylation in the presence of TNF receptor-associated factor 2 (TRAF2) and intracellular isoform of osteopontin (iOPN) whereas TLR4 signaling provides IFN regulatory factor 5 (IRF5) as a chaperone for sumoylated IRAK1 nuclear translocation. Interaction of T cells with macrophages was observed in the spleen in vivo after endotoxemia induction with LPS injection. Our study demonstrates a mechanistic basis for the immunosuppressive role of macrophage CD40 in LPS endotoxemia.OPN | CD40L | CD154 | simultaneous stimulation | T cell migration

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Section: T Cells Have a Protective Role In Lps Endotoxemia By Down-mentioning

confidence: 96%

T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation

Inoue¹,

Arikawa²,

Chen³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Moore, Silliman, and others (52)(53)(54) have shown that PAF is a primary agent responsible for neutrophil priming in human trauma victims. In contrast, LPS and TNF␣ are the likely priming agents in acute pancreatitis (55,56), as well as in many patients with sepsis (57)(58)(59)(60)(61), and these agents have been directly implicated in causing acute lung injury (62)(63)(64)(65) and ischemia-induced acute renal failure (66).…”

mentioning

confidence: 99%

Distinct Ligand-dependent Roles for p38 MAPK in Priming and Activation of the Neutrophil NADPH Oxidase

Brown

Stewart

Bissonnette

et al. 2004

Journal of Biological Chemistry

103

108

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In response to certain cytokines and inflammatory mediators, the activity of the neutrophil NADPH oxidase enzyme is primed for enhanced superoxide production when the cells receive a subsequent oxidase-activating stimulus. The relative role of p38 MAPK in the priming and activation processes is incompletely understood. We have developed a 2-step assay that allows the relative contributions of p38 MAPK activity in priming to be distinguished from those involved in oxidase activation. Using this assay, together with in vitro kinase assays and immunochemical studies, we report that p38 MAPK plays a critical role in TNF␣ priming of the human and porcine NADPH oxidase for superoxide production in response to complement-opsonized zymosan (OpZ), but little, if any, role in neutrophil priming by platelet-activating factor (PAF) for OpZ-dependent responses. The OpZ-mediated activation process per se is independent of p38 MAPK activity, in contrast to oxidase activation by fMLP, where 70% of the response is eliminated by p38 MAPK inhibitors regardless of the priming agent. We further report that incubation of neutrophils with TNF␣ results in the p38 MAPK-dependent phosphorylation of a subpopulation of p47 phox and p67 phox molecules, whereas PAF priming results in phosphorylation only of p67 phox . Despite these phosphorylations, TNF␣ priming does not result in significant association of either of these oxidase subunits with neutrophil membranes, demonstrating that the molecular basis for priming does not appear to involve preassembly of the NADPH oxidase holoenzyme/cytochrome complex prior to oxidase activation.The neutrophil NADPH oxidase is a multiprotein enzyme that catalyzes the production of O 2 Ϫ from oxygen using NADPH as an electron donor (1, 2). The O 2 Ϫ is subsequently converted to powerful oxidizing agents such as hypohalides, singlet oxygen, peroxides, and chloramines, which together with proteases and ions, are primarily responsible for neutrophil-mediated killing of microorganisms (2-4). These oxidase products, however, are also highly destructive to nearby tissues (see Refs. 5-7). Consequently, tight temporal and spatial regulation of the oxidase is required so that it is activated only under appropriate circumstances.The NADPH oxidase holoenzyme consists of 6 subunits. In resting cells in which the oxidase is dormant, 4 of the subunits, p47 phox , p67 phox , p40 phox , and the small GTPase Rac2 are localized exclusively in the cytoplasm whereas the remaining two subunits, p22 phox and gp91 phox form a heterodimeric membrane-bound flavocytochrome known as cytochrome b 558 . Exposure of neutrophils to a variety of diverse stimuli results in translocation and docking of the cytosolic subunits with the membrane subunits (3, 8 -19), allowing electrons to flow from p67 phox -bound NADPH to molecular oxygen via an FAD moiety and two heme groups in the membrane-bound cytochrome (20). The subunit translocation and oxidase activation process is complex and requires multisite phosphorylation of the cytosolic subuni...

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“…TNF-· has been shown to be an important initiator of local and systemic damage occurring in AP and the blocking of the action of this cytokine has been shown to delay the onset of AP (9). Additionally, serum TNF-· levels have been found to be correlated with the severity of AP in humans (28). IL-1ß has been shown to be a significant cytokine for the development of AP and the inhibition of its production has been shown to decrease the severity of AP (29,30).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of Curcuma longa against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury

Seo¹,

Bae²,

Kim³

et al. 2010

Int J Mol Med

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Abstract. Curcuma longa (CL) has been reported to possess a variety of pharmacological activities. However, the effects of CL on acute pancreatitis (AP) have not yet been determined. To this end, we examined the effects of CL on ceruleininduced AP. Cell viability and cytokine productions were measured in pancreatic acini. Mice were divided into 3 groups: i) Normal group, ii) normal saline-treated group, iii) group treated with CL at a dose of 0.05, 0.1, 0.5 and 1 g/kg. CL was administered orally to mice for 7 days. The mice were intraperitoneally injected with the stable cholecystokinin analogue, cerulein (50 μg/kg), every hour for a total of 6 h. The mice were sacrificed 6 h after the completion of the cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphological examination, measurement of tissue myeloperoxidase activity, as well as the level of cytokines and heme oxygenase-1 (HO-1). The CL treatment reduced cerulein-induced cell death and cytokine production in pancreatic acini. The administration of CL significantly ameliorated the severity of pancreatitis and pancreatitisassociated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization, necrosis, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as interleukin (IL)-1ß and -6 and tumor necrosis factor (TNF)-·. In order to identify the regulatory mechanism of CL on cerulein-induced pancreatitis, we examined the level of HO-1 in the pancreas. We found that the administration of CL induced HO-1. Our results suggest that CL plays a protective role in the development of AP and pancreatitisassociated lung injury.

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Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe acute pancreatitis.

Cited by 186 publications

References 24 publications

T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation

T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation

Distinct Ligand-dependent Roles for p38 MAPK in Priming and Activation of the Neutrophil NADPH Oxidase

Protective effects of Curcuma longa against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury

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