The ST2 Pathway Is Involved in Acute Pancreatitis A Translational Study in Humans and Mice
| Autor: | Ouziel, Romy, Gustot, Thierry, Moreno, Christophe, Arvanitakis, Marianna, Degré, Delphine, Trepo, Eric, Quertinmont, Eric, Vercruysse, Vincent, Demetter, Pieter, Le Moine, Olivier, McKenzie, Andrew, Delhaye, Myriam, Devière, Jacques, Lemmers, Arnaud |
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| Jazyk: | angličtina |
| Předmět: | |
| Zdroj: | The American journal of pathology, 180 (6 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2012.03.009 |
| Popis: | Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathways are not clearly elucidated. Activation of interleukin 1β (IL-1β) and immunomodulation via MyD88, the first signaling molecule in the ST2 pathway, seem to be involved. Because IL-33, the ST2 ligand, is an IL-1 family member and acts as an alarmin, we explored the ST2 pathway in human and mouse AP. Soluble ST2 was assayed by enzyme-linked immunosorbent assay (ELISA) in plasma of 44 patients admitted for AP. The levels of soluble ST2 increased early during AP and correlated with parameters of severity. Under two different experimental models of AP (ie, choline-deficient-ethionine-supplemented diet and cerulein injections), ST2-deficient mice (Il1rl1(-/-)) presented with more severe disease than wild-type mice, with increased activation of mast cells. In vitro, Il1rl1(-/-) bone-marrow-derived mast cells exhibited exacerbated degranulation, compared with the wild type. Flow cytometry identified mast cells as the main peritoneal population expressing ST2. Using immunohistochemistry and ELISA, we showed constitutive expression of IL-33 in murine pancreas and its release during experimental AP. Correlated with AP severity, increased soluble ST2 levels evoke involvement of the ST2 pathway in human AP. Furthermore, our experimental data suggest a protective role for ST2 during AP, highlighting the potential regulatory role of mast cells and the possibility of the ST2 pathway as a new therapeutic target in AP. JOURNAL ARTICLE SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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