کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3293877 | 1209828 | 2012 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Aryl Hydrocarbon Receptor Regulates Pancreatic IL-22 Production and Protects Mice From Acute Pancreatitis Aryl Hydrocarbon Receptor Regulates Pancreatic IL-22 Production and Protects Mice From Acute Pancreatitis](/preview/png/3293877.png)
Background & AimsThe type of immune response during development of acute pancreatitis (AP) determines disease severity. Pancreatic epithelial cells express the interleukin (IL)-22 receptor A1 (IL-22RA1). The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that regulates expression of IL-22. We investigated sources and role of IL-22 in the pancreas, along with the effects of AhR activation on IL-22 expression and AP progression in mice.MethodsWe analyzed the effects of recombinant IL-22, a monoclonal antibody against IL-22, and agonists and antagonists of AhR in mice with AP (induced with caerulein or a choline-deficient diet supplemented with DL-ethionine) and control mice. We also analyzed transgenic mice with AhR deficiency (AhRd and AhR−/− mice).ResultsCD4+ T cells were the main source of IL-22 in pancreatic tissues from healthy mice. During development of AP, numbers of IL-22+ CD4+ T cells were reduced, whereas IL-22RA1 was up-regulated. Consistent with high levels of IL-22RA1 expression, pancreatic acinar cells responded to IL-22 signaling via signal transducers and activators of transcription 3; administration of IL-22 reduced AP and associated lung injury in mice. AhR was required for production of IL-22 and protected mice from AP. Mice that did not respond to AhR activation developed AP, but administration of IL-22 reduced AP; blockade of IL-22 reversed the ability of activated AhR to protect against AP.ConclusionsAhR activation protects mice from AP by inducing expression of IL-22. AhR therefore mediates interactions between pancreatic leukocytes and epithelial cells and might be developed as a therapeutic target.
Journal: Gastroenterology - Volume 143, Issue 6, December 2012, Pages 1670–1680