1. Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, 200092, Shanghai, China.
2. Department of General, Visceral, and Transplantation Surgery, University Hospital, LMU Munich, 81377, Munich, Germany.
3. Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia.
4. Department of Cell Signaling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia.
5. Department of Histology, Embryology and Cytology, Azerbaijan Medical University, Baku, Azerbaijan.
6. German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany.
* Sisi Lin and Florian Kühn contributed equally to this study.
Rationale: Postoperative ileus (POI) is a frequent complication arising after gastrointestinal surgery but pathogenesis of POI is still not fully understood. While Th1 immune cells are implicated in POI, the involvement of Th2 cells has not yet been clarified. Given the impact of reactive oxygen species (ROS) in the regulation of Th1 and Th2 balance, we hypothesized that not only Th1 but also Th2 immune response can be involved in the development of experimental POI.
Methods: The intestinal transit test was performed using carbon gum arabic. Electron microscopy was employed to assess tissue morphology and the presence of immune cells. Cytokines, IgE and ROS were measured. Immune cells from Peyer's patches were analyzed by Flow Cytometry and toluidine blue staining was used for detection of mast cells. Transcriptional factors were analyzed by Western blot.
Results: POI is associated with an increase in both Th2 cytokines and Th2 cells. We have further demonstrated that POI induces a Th2-dependent activation of memory and non-memory B cells. This was accompanied by an increase in a number of mast cells in the colon of POI mice as well by an increased IgE and histamine plasma levels. We found that POI-induced accumulation of ROS was associated with an increased expression of the transcriptional factors HMBGI, NF-κB, and p38. This increased expression seemed to be associated with a Th2 response.
Conclusion: Th2 immune response can be involved in the activation of mast cells in POI, which was associated with ROS mediated activation of NF-κB and p38 MAPK signaling pathway.
Keywords: Postoperative Ileus, Th2 Cells, ROS, Mast Cells, IgE