title: MyD88-dependent interleukin-10 production from regulatory CD11b⁺Gr-1(high) cells suppresses development of acute cerulein pancreatitis in mice.
abstract: We explored the role of the MyD88 signaling pathway. This pathway mediates the recognition of pathogen-associated molecular patterns and damage-associated molecular patterns via Toll-like receptors (TLRs) and/or IL-1/IL-18 via each cytokine receptor in a murine model of acute pancreatitis induced by cerulein administration. Our analysis revealed that: various TLRs and MyD88 molecules were constitutively expressed in the pancreas of cerulein-treated and untreated wild-type (WT) mice. MyD88⁻/⁻ mice administered cerulein developed severe pancreatitis as compared with MyD88⁺/⁺ WT mice. The number of IL-10-expressing CD11b⁺Gr-1(high) cells in cerulein-administered MyD88⁻/⁻ mice was significantly decreased. This was in accordance with a reciprocal increase in the infiltration of CD4⁺ T cells as compared with that in control MyD88⁺/⁺ mice. WT mice pretreated with antibiotics and administered cerulein developed milder pancreatitis as compared with control cerulein-administered mice without antibiotic treatment. The MyD88 signaling pathway contributes to the induction of regulatory IL-10-producing macrophages/myeloid-derived suppressor cells, possibly in response to non-bacterial components in the damaged pancreas. These results provide a new concept for therapeutic strategies against acute pancreatitis.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Koike
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Keita
authors.initials: K
authors.lastname: Saeki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masaru
authors.initials: M
authors.lastname: Nakano
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mikami
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamagishi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakamoto
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Ebinuma
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D039481:CD11b Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002108:Ceruletide; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000096:biosynthesis*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D039481:CD11b Antigen; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C551746:granulocyte receptor 1, mouse; D016753:Interleukin-10; D008795:Metronidazole; D014640:Vancomycin; D000667:Ampicillin; D002108:Ceruletide; D009355:Neomycin