| First Author | Hupa KJ | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 10602 |
| PubMed ID | 31332247 | Mgi Jnum | J:285919 |
| Mgi Id | MGI:6387758 | Doi | 10.1038/s41598-019-46968-1 |
| Citation | Hupa KJ, et al. (2019) AIM2 inflammasome-derived IL-1beta induces postoperative ileus in mice. Sci Rep 9(1):10602 |
| abstractText | Postoperative ileus (POI) is an intestinal dysmotility frequently occurring after abdominal surgery. An orchestrated neuroimmune response within the muscularis externa (ME) involves activation of resident macrophages, enteric glia and infiltration of blood-derived leukocytes. Interleukin-1 receptor type-I (IL1R1) signalling on enteric glia has been shown to be involved in POI development. Herein we investigated the distinct role of the IL1R1 ligands interleukin (IL) -1alpha and IL-1beta and focused on the mechanism of IL-1beta production. IL-1alpha and IL-1beta deficient mice were protected from POI. Bone-marrow transplantation studies indicated that IL-1alpha originated from radio-resistant cells while IL-1beta was released from the radio-sensitive infiltrating leukocytes. Mouse strains deficient in inflammasome formation identified the absent in melanoma 2 (AIM2) inflammasome to be crucial for IL-1beta production in POI. Mechanistically, antibiotic-treated mice revealed a prominent role of the microbiome in IL-1beta production. Our study provides new insights into distinct roles of IL-1alpha and IL-1beta signalling during POI. While IL-1alpha release is most likely an immediate passive response to the surgical trauma, IL-1beta production depends on AIM2 inflammasome formation and the microbiome. Selective interaction in this pathway might be a promising target to prevent POI in surgical patients. |
