CD4+ T cells play an important role in acute experimental pancreatitis in mice

Demols, A.; Moine, Olivier Le; Desalle, Fabrice; Quertinmont, Eric; Laethem, Jean‐Luc Van; Devière, Jacques

doi:10.1016/s0016-5085(00)70265-4

Cited by 144 publications

(104 citation statements)

References 40 publications

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“…44 Control mice were injected with an equivalent volume of control reagent, as described earlier. Liver harvesting was performed 1 week after T-cell transfer.…”

Section: Determination Of Cd40 Ligand and ␤-Actin Messenger Rna Levelmentioning

confidence: 99%

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

et al. 2000

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Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-␥) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemiareperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-␥ were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-␥ release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-␥ release (؊66% or ؊41%, ؊95% or ؊94%, and ؊70% or ؊70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell-and macrophage-dependent cytokines. (HEPATOLOGY 2000;31:1266-1274.)

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“…44 Control mice were injected with an equivalent volume of control reagent, as described earlier. Liver harvesting was performed 1 week after T-cell transfer.…”

Section: Determination Of Cd40 Ligand and ␤-Actin Messenger Rna Levelmentioning

confidence: 99%

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

et al. 2000

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“…Demols et al (17) demonstrated that the administration of CD4-positive T cells into nude mice partially exaggerated the severity of cerulein-induced acute pancreatitis, presumably due to IFN-␥ production by adoptively transferred cells, but they did not clarify the effects of the adoptive transfer on neutrophil infiltration. Moreover, accumulating evidence indicates the essential contribution of cyclooxygenase-2 (COX-2) 3 to cerulein-induced acute pancreatitis, because inhibition of the COX-2 pathway also ameliorates pancreatitis (18).…”

mentioning

confidence: 99%

IFN-γ Protects Cerulein-Induced Acute Pancreatitis by Repressing NF-κB Activation

Hayashi

Ishida

Kimura

et al. 2007

The Journal of Immunology

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We explored the pathophysiological roles of IFN-γ in cerulein-induced acute pancreatitis. In wild-type (WT) mice, cerulein injection caused acute pancreatitis as evidenced by increased serum amylase levels and pathological changes such as interstitial edema, vacuolization, acinar cell necrosis, and neutrophil infiltration in pancreas. Concomitantly, cerulein treatment augmented intrapancreatic gene expression of TNF-α, KC/CXCL1, MIP-2/CXCL2, cyclooxygenase-2 (COX-2), and IFN-γ in WT mice. In situ hybridization combined with immunofluorescence analyses demonstrated that infiltrating neutrophils expressed IFN-γ mRNA. Unexpectedly, IFN-γ−/− mice exhibited exacerbated cerulein-induced pancreatic injury, with enhanced neutrophil recruitment. Moreover, intrapancreatic gene expression of TNF-α, KC/CXCL1, MIP-2/CXCL2, and COX-2 were significantly exaggerated in IFN-γ−/− mice, compared with WT mice. Cerulein activated NF-κB, an indispensable transcription factor for gene transcription of TNF-α, KC/CXCL1, MIP-2/CXCL2, and COX-2, in pancreas of cerulein-treated WT mice as evidenced by the increases in nuclear amount and DNA-binding activity of NF-κB p65. In comparison with WT mice, IFN-γ−/− mice exhibited exaggerated and prolonged NF-κB activation, probably due to reduced acetylation of Stat1, a main signal transducer of IFN-γ, because acetylated Stat1 can inhibit NF-κB activation. Indeed, IFN-γ acetylated Stat1 and reciprocally reduced NF-κB activation and COX-2 expression in neutrophils. Finally, even when administered 4 h after the first cerulein injection, IFN-γ remarkably attenuated acute pancreatitis in both WT and IFN-γ−/− mice, with reduced NF-κB activation and COX-2 expression. Thus, IFN-γ can have anti-inflammatory effects on acute pancreatitis by depressing the proinflammatory consequences of NF-κB activation.

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“…Demols et al showed that T lymphocytes, particularly CD4+ T-cells, play a central role in cerulein pancreatitis. These results indicate that both neutrophils and lymphocytes contribute to pancreatitis [44].…”

Section: Discussionmentioning

confidence: 66%

TNF-α Regulated MAdCAM-1 Expression in Pancreatic Microvessel Endothelium: A Possible Role for MAdCAM-1 in Pancreatitis?

Ando¹,

Jordan²,

Wang³

et al. 2008

TOGASJ

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Abstract:The Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) is associated with active inflammatory bowel disease; however MAdCAM-1 expression in the pancreas has not been previously documented. This study investigated MAdCAM-1 expression during cerulein-induced pancreatitis, and examined MAdCAM-1 expression, regulation and function in cytokine-treated pancreatic endothelial cells. Acute pancreatitis was induced by serial injections of cerulein over 10h, at which point tissue samples were collected. Pancreas endothelial cells (PMEC) were prepared from H2Kb-tsA58 (Immortomouse) mice. MAdCAM-1 expression was examined by immunoblotting after cytokine (TNF-, ILor IFN-) stimulation. 2 nd messages regulating MAdCAM-1 were studied by adding pharmacological blockers prior to cytokines. MAdCAM-1 dependent lymphocyte adhesion was monitored using 4 7-integrin expressing lymphocytes. In cerulein-pancreatitis, MAdCAM-1 was upregulated by 10h, and closely correlated with histopathology. In PMEC, only TNF-induced MAdCAM-1 dose (0-20ng/ml) and time (>12h-48h) dependently. MAdCAM-1 expression was PKC, tyrosine kinase, p38 MAPK, and NF-B-PARP dependent. PMEC-lymphocyte adhesion was increased by TNF-, and significantly reduced by MAdCAM-1 antibody. MAdCAM-1 is induced in the inflamed pancreas, and in TNF-stimulated PMEC, and may represent a novel determinant of pancreatic-lymphocyte recruitment in inflammation. PMEC cells might provide a useful system to study mechanisms related to both acute and chronic pancreatitis.

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CD4+ T cells play an important role in acute experimental pancreatitis in mice

Cited by 144 publications

References 40 publications

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

IFN-γ Protects Cerulein-Induced Acute Pancreatitis by Repressing NF-κB Activation

TNF-α Regulated MAdCAM-1 Expression in Pancreatic Microvessel Endothelium: A Possible Role for MAdCAM-1 in Pancreatitis?

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