| First Author | Banerjee S | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 13953 |
| PubMed ID | 31562350 | Mgi Jnum | J:284293 |
| Mgi Id | MGI:6389547 | Doi | 10.1038/s41598-019-49437-x |
| Citation | Banerjee S, et al. (2019) C/EBPdelta protects from radiation-induced intestinal injury and sepsis by suppression of inflammatory and nitrosative stress. Sci Rep 9(1):13953 |
| abstractText | Ionizing radiation (IR)-induced intestinal damage is characterized by a loss of intestinal crypt cells, intestinal barrier disruption and translocation of intestinal microflora resulting in sepsis-mediated lethality. We have shown that mice lacking C/EBPdelta display IR-induced intestinal and hematopoietic injury and lethality. The purpose of this study was to investigate whether increased IR-induced inflammatory, oxidative and nitrosative stress promote intestinal injury and sepsis-mediated lethality in Cebpd(-/-) mice. We found that irradiated Cebpd(-/-) mice show decreased villous height, crypt depth, crypt to villi ratio and expression of the proliferation marker, proliferating cell nuclear antigen, indicative of intestinal injury. Cebpd(-/-) mice show increased expression of the pro-inflammatory cytokines (Il-6, Tnf-alpha) and chemokines (Cxcl1, Mcp-1, Mif-1alpha) and Nos2 in the intestinal tissues compared to Cebpd(+/+) mice after exposure to TBI. Cebpd(-/-) mice show decreased GSH/GSSG ratio, increased S-nitrosoglutathione and 3-nitrotyrosine in the intestine indicative of basal oxidative and nitrosative stress, which was exacerbated by IR. Irradiated Cebpd-deficient mice showed upregulation of Claudin-2 that correlated with increased intestinal permeability, presence of plasma endotoxin and bacterial translocation to the liver. Overall these results uncover a novel role for C/EBPdelta in protection against IR-induced intestinal injury by suppressing inflammation and nitrosative stress and underlying sepsis-induced lethality. |
