Plasma Non-transferrin-Bound Iron Could Enter into Mice Duodenum and Negatively Affect Duodenal Defense Response to...

Plasma non-transferrin-bound iron (NTBI) exists when the plasma iron content exceeds the carrying capacity of transferrin and can be quickly cleared by the liver, pancreas, and other organs. However, whether it could enter the small intestine and its effects still remain unclear. Herein, these issues were explored. Mice were intravenously administrated of ferric citrate (treatment) or citrate acid (control) 10 min after the saturation of the transferrin. Two hours later, hepatic, duodenal, and jejunal iron content and distribution were measured and duodenal transcriptome sequencing was performed. Significant increase of duodenal and hepatic iron content was detected, indicating that plasma NTBI could be absorbed by the duodenum as well as the liver. A total of 103 differentially expressed genes were identified in the duodenum of mice in the treatment group compared to the control group. Gene Ontology (GO) functional analysis of these genes showed that they were mainly involved in defense response to virus and immune response. The results of Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis revealed that there were major changes in the hematopoietic cell lineage and some virus infection pathways between the two groups. Determination of 7 cytokines in the duodenum were further conducted, which demonstrated that the anti-inflammatory factors interferon (IL)-4 and IL-10 in the duodenum were significantly decreased after NTBI uptake. Our findings revealed that NTBI in plasma can enter the duodenum, which would change the duodenal hematopoietic cell lineage and have a negative impact on defense response to the virus and immune responses.