role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in il-10-deficient mice肥大细胞在炎症性肠病中的作用和炎症反应的结直肠肿瘤il-10-deficient老鼠.pdfVIP

Role of Mast Cells in Inflammatory Bowel Disease and Inflammation-Associated Colorectal Neoplasia in IL-10-Deficient Mice 1 1 1,2,3 1,4 Maciej Chichlowski , Greg S. Westwood , Soman N. Abraham , Laura P. Hale * 1 Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America, 2 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America, 3 Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America, 4 The Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America Abstract Background: Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens. Methodology/Principal Findings: This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro- inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il102/ 2 mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-c mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il102/ 2