title: The ST2 pathway is involved in acute pancreatitis: a translational study in humans and mice.
abstract: 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.
authors.affiliation: Laboratory of Experimental Gastroenterology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Romy
authors.initials: R
authors.lastname: Ouziel
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.forename: Marianna
authors.initials: M
authors.lastname: Arvanitakis
authors.forename: Delphine
authors.initials: D
authors.lastname: Degré
authors.forename: Eric
authors.initials: E
authors.lastname: Trépo
authors.forename: Eric
authors.initials: E
authors.lastname: Quertinmont
authors.forename: Vincent
authors.initials: V
authors.lastname: Vercruysse
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Moine
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Myriam
authors.initials: M
authors.lastname: Delhaye
authors.forename: Jacques
authors.initials: J
authors.lastname: Devière
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lemmers
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015550:Cell Degranulation / Q000502:physiology; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology; D010529:Peritoneal Cavity / Q000166:cytology; D011956:Receptors, Cell Surface / Q000097:blood* / Q000502:physiology; D018123:Receptors, Interleukin / Q000172:deficiency / Q000502:physiology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: C079241:IL1RL1 protein, human; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin