Project description:Alternatively-activated macrophages (M2) are known to play a critical role in intestinalization of spasmolytic polypeptide-expressing metaplasia (SPEM), which is a precursor to gastric adenocarcinoma. However, the precise mechanism(s) and critical mediators produced by M2 macrophages that lead to SPEM are unknown. Using established murine models of metaplasia in the stomach, the aim of the present study was to determine how M2 macrophages induce intestinalized SPEM. Macrophages from the stomach corpus of mice with SPEM (DMP-777-treated) or advanced intestinalized SPEM (L635-treated) were isolated and RNA sequencing was performed. IL-33 was the most upregulated cytokine in macrophages associated with intestinalized SPEM. L635-treated IL-33 knock out mice did not develop metaplasia, suggesting that IL-33 is required for the induction of SPEM after acute parietal cell loss. While the loss of IL-33 did not reduce macrophage recruitment into the mucosa, infiltrating macrophages were not M2 polarized. We conclude that IL-33 is necessary for both the induction of mucous metaplasia (SPEM) in the stomach and polarization towards M2 in recruited macrophages. Our data suggest that the inflammatory pathway in the stomach after parietal cell loss resembles pathways associated with allergy-induced airway inflammation, which implicates novel treatment options for gastritis patients to prevent gastric cancer.
Project description:Graft-versus-Host Disease (GvH) is the excessive inflammatory response by mature T cells contained in the graft during bone marrow transplantation. The allogeneic T cells recognize self-antigens as foreign and systemically attack multiple organs mostly with epithelial structures such as the skin, liver and gastrointestinal tract. We could show that IL-33 administration during allogeneic hematopoietic cell transplantation (alloHCT) increased regulatory T cell (Treg) numbers and ameliorated the outcome of GvHD. Furthermore, it is known that IL-33 also has an impact on myeloid cell compartments and we showed that IL-33 delivery together with a loss of FoxP3 positive Treg led to a massive expansion of myeloid cells. With the underlying experiment we wanted to further characterize the myeloid cells when Treg are lost, therefore mice were treated with IL-33 and one group had a loss in FoxP3 cells. CD11b+F4/80+Gr-1lo myeloid cells were sorted and analyzed in the microarray. The examined myeloid cell population shows strong activation of the IFNg transcriptome and are prone to M1 macrophage polarization. Therefore, Treg restrain myeloid cell expansion and polarization during IL-33 delivery.
Project description:Using the highly sensitive miRNA microarray, we screened 107 up-regulated microRNAs and 33 down-regulated microRNAs in the INT-HA-induced M2-like macrophages and we explored the functions of these miRNAs in macrophage polarization. The enrichment results indicated that these miRNAs might participate in the process of macrophage polarization. Furthermore, the quantitative real-time polymerase chain reaction results showed that miR-935 may play an important role in M2 macrophage polarization which was activated by INT-HA.
Project description:Hypoxia promotes macrophage polarization triggered by IL-6.In an attempt to gain speci?c insight into the mechanism of macrophage polarization during hypoxia. We used microarrays to detail the global programme of gene expression and identified distinct classes of changed genes during this process. Four groups of RAW264.7 cells were harvested for RNA extraction and hybridization on Affymetrix microarrays (normoxia control, normoxia+IL-6,hypoxia control,hypoxia+IL-6).
