Involvement of nuclear factor erythroid 2-related factor 2 in neonatal intestinal interleukin-17D expression in hyperoxia

Interleukin 17D (IL-17D) plays an important role in host defense against inflammation and infection. In the present study, the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating the production of IL-17D was investigated under hyperoxia. For this purpose, neonatal rats were randomized into two groups; the model group was exposed to hyperoxia (80-85% O-2), while the control group was maintained under normoxic conditions (21% O-2). Small intestine tissue was collected on postnatal days 3, 7, 10 and 14. IL-17D expression was detected by immunofluorescence, immunohistochemistry and western blotting. The levels of Nrf2 and kelch-like ECH-associated protein 1 (keap1) were detected by immunohistochemistry and western blotting. Results showed that IL-17D expression in intestine epithelial cells increased steadily, reaching a peak on day 7, and decreased gradually on days 10 and 14 under hyperoxia. Nrf2 expression was consis-tent with IL-17D, and it was positively correlated with IL-17D. However, on postnatal days 10 and 14, the number of CD4(+) T cells and CD19(+) B cells expressing IL-17D was increased, and positive cells of the model group were significantly more than that of the control group. Keap1 levels were lower at the early stage. In conclusion, the expression levels of intestinal IL-17D and Nrf2 were altered simultaneously following neonatal rat development in hyperoxia, indicating that Nrf2 may be involved in regulating the expression of IL-17D in intestinal epithelial cells. Moreover, IL-17D in intestinal epithelial cells may play a unique immunological role during hyperoxia.