| First Author | Li X | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 11 | Pages | 165901 |
| PubMed ID | 32711051 | Mgi Jnum | J:300992 |
| Mgi Id | MGI:6504158 | Doi | 10.1016/j.bbadis.2020.165901 |
| Citation | Li X, et al. (2020) 6-Formylindolo (3, 2-b) Carbazole (FICZ)-mediated protection of gut barrier is dependent on T cells in a mouse model of alcohol combined with burn injury. Biochim Biophys Acta Mol Basis Dis 1866(11):165901 |
| abstractText | 6-Formylindolo (3, 2-b) Carbazole (FICZ) is a ligand of aryl hydrocarbon receptor (AHR) which regulates Th17 release of IL-17 and IL-22 production. Earlier, we showed that ethanol combined with burn injury suppresses Th17 responses and disrupts intestinal barrier leading to increased gut bacterial growth and translocation. Since IL-22 is known for its role in intestinal barrier maintenance, we determined whether treatment of mice with FICZ restores T cell IL-22 release and protects intestine barrier following ethanol and burn injury. Wildtype and Rag1-/- mice were gavaged with ~2.9 g/kg ethanol or water, and given a ~12.5% total body surface area burn. Mice were given FICZ (5 mug) in resuscitation fluid. FICZ treatment of wildtype mice normalized IL-22 and IL-17 in lamina propria and spleen T cells, as well as increased CYP1A1 expression in spleen T cells. This was accompanied by improved gut motility, decreased copy number of small intestine total bacteria and Enterobacteriaceae, attenuation of intestinal tissue levels of IL-6, KC, IL-18, decreased apoptosis, and prevention of gut leakiness following ethanol and burn injury. However, FICZ treatment of Rag1-/- mice did not improve any of the parameters listed after ethanol and burn injury. Additional data generated using mice treated with recombinant IL-22 alone or in combination with anti-IL-18 antibody suggest that full protection of gut barrier integrity requires both IL-18 inhibition and IL-22 restoration following ethanol and burn injury. Together our findings suggest that AHR ligand FICZ may have better therapeutic potential for maintenance of gut barrier function after ethanol and burn injury. |
