Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8434142 | Cancer Letters | 2018 | 11 Pages |
Abstract
Intestinal myeloid cells are not only essential for keeping local homeostasis, but also play an important role in regulating the occurrence of colitis and colitis-associated cancer (CAC). In these diseases, the manner in which the myeloid cells work and which molecular pathways influence them are still not fully understood. In our study, we discovered that MyD88 signaling in colonic myeloid cells participates in the development of CAC. Myeloid MyD88-deficient mice showed greater susceptibility to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC, as evidenced by the increase in the number and sizes of tumors. Myeloid MyD88 deletion markedly increased production of pro-inflammatory and pro-tumor cytokines; recruitment of more IL-1β producing-neutrophils in colon from bone marrow; increased in epithelial cell apoptosis and decreased in epithelial cell proliferation; enhancement of colon mucosal expression of COX-2, p-STAT3, β-catenin, and cyclinD1; induction of further DNA damage and β-catenin mutation. To sum up, these results suggest that myeloid MyD88 signaling protects the intestine from tumorigenesis during the development of CAC.
Keywords
IBDAREGMLNLSKTLRHIF-1αazoxymethaneAOMCOX-2myeloid progenitorsATRDSSMYD88CACataxia telangiectasia mutatedataxia telangiectasia and Rad3 relatedamphiregulinChronic inflammationInflammatory bowel diseaseToll-like receptorLineageATMcolitis-associated cancerColitis-associated colorectal cancerMyeloid cellsdextran sodium sulfateCyclooxygenase-2Spleenhypoxia-inducible factor-1αmyeloid differentiation factor 88Lamina propriaLinbone marrowknock outwild typemesenteric lymph node
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Authors
Junhua Song, Zhengtao Chen, Tingting Geng, Meixiang Wang, Shuying Yi, Kai Liu, Wei Zhou, Jiming Gao, Wengang Song, Hua Tang,