Postoperative ileus involves interleukin-1 receptor signaling in enteric glia
Burkhard Stoffels1, Kristof Johannes Hupa1, Susanne A Snoek2
1Department of Surgery, University of Bonn, Bonn, Germany.
Gastroenterology
|September 27, 2013
Summary
Interleukin-1 (IL-1) signaling through IL-1 receptor 1 (IL-1R1) is crucial for the development of postoperative ileus (POI) in mice. Blocking IL-1 signaling may offer a therapeutic strategy for treating POI.
Area of Science:
- Gastroenterology
- Immunology
- Surgical Pathology
Background:
- Postoperative ileus (POI) is a frequent complication following abdominal surgery, leading to increased morbidity.
- Understanding the underlying immune mechanisms of POI is essential for developing effective treatments.
Purpose of the Study:
- To investigate the cellular mechanisms and immune responses involved in the pathogenesis of POI.
- To identify key molecular pathways regulating POI development.
Main Methods:
- A mouse model of POI induced by intestinal manipulation was utilized.
- Studies involved genetically modified mice lacking specific Toll-like receptors (TLRs), MyD88, and IL-1 signaling components (IL-1R1, IL-18).
- Bone marrow transplantation experiments were conducted to elucidate the role of hematopoietic and non-hematopoietic cells.
Main Results:
- POI development was dependent on MyD88 and IL-1 receptor 1 (IL-1R1), but not TLRs 2, 4, or 9.
- Mice lacking IL-1R1 did not develop POI, and blockade of IL-1α and IL-1β protected against POI.
- IL-1R1 activation in non-hematopoietic cells, specifically enteric glial cells, was required for POI.
- Human tissue samples confirmed IL-1R1 expression in the myenteric plexus.
Conclusions:
- IL-1 signaling, mediated by IL-1R1 and MyD88, is a critical pathway in the development of POI.
- Targeting the IL-1 signaling pathway presents a promising therapeutic avenue for managing POI.
Keywords:
GFAPGIGastrointestinal DysmotilityILIL-1 receptor antagonistIL-18RIL-1RIL-1R1IL-1raIMIgInflammatory ResponseInnate ImmunityMCP-1MEMPOPOIPathogen RecognitionTLRToll-like receptorWTgastrointestinalglial fibrillary acidic proteinimmunoglobulininterleukininterleukin 1 receptorinterleukin-1 receptor type Iinterleukin-18 receptorintestinal manipulationmRNAmessenger RNAmonocyte chemotactic protein 1muscularis externamyeloperoxidasepostoperative ileuswild-type
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