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Chemotherapy modulates intestinal immune gene expression in piglets including surfactant protein-D and DMBT1

ABSTRACT: Cytotoxic therapy leads to marked changes in intestinal structure, function, immunity and microbiota. Information about chemotherapy-induced intestinal gene expression may provide insights into the mechanisms underlying gut toxicity, and help to identify biomarkers and targets for intervention. We investigated jejunal tissue from piglets subjected to two different, clinically-relevant chemotherapy regimens, 1) busulfan plus cyclophosphamide (BUCY) and 2) doxorubicin (DOX). Gene expression analysis identified 1328 and 594 differentially expressed genes in the BUCY and DOX pigs, compared with their respective controls. Similar changes in expression patterns across BUCY and DOX piglets were found for 137 genes (95 genes repressed and 42 induced). Selected genes of potential biological significance were confirmed by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D (SP-D), deleted in malignant brain tumors 1 (DMBT-1) and peptidoglycan recognition protein 2 (PGLYRP2) were among the up-regulated genes for both chemotherapy treatments. Based on the results from the two different treatments, we conclude that chemotherapy induces reduced intestinal adaptive immunity while innate immune functions involved in surveillance, protection and homeostasis of mucosal surfaces are up-regulated. The results may be of value to understand monitor and prevent chemotherapy-induced intestinal mucositis by dietary or medical interventions.

ORGANISM(S): Sus scrofa

PROVIDER: GSE71964 | GEO | 2018/07/01

REPOSITORIES: GEO

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Project description:Development of immune competence in pigs is important for resilience, disease resistance, and performance later in life. Dietary interventions in early life can contribute to immune system development. Use of model dietary interventions, such as diets with a high concentration of zinc, can contribute to the understanding of the interactions between the diet, the intestinal microbiota and intestinal tissues. The aim of the present study was to evaluate the effects of provision of a diet with a high concentration of zinc (Zn, 2690 mg/kg), as model intervention, as compared to provision of a control diet with a regular Zn concentration (100 mg/kg) during a period of nine days during the post weaning period (d 14-23 post weaning (pw)), on the composition of the intestinal microbiota and gene expression in the intestinal mucosa on d 23 and 35 pw (12 d after the termination of the Zn intervention). Whole genome gene expression analysis of the jejunal and ileal mucosa revealed a small overall time-treatment interaction effect at d 23 pw in both intestinal tissues. In both jejunal and ileal mucosa various genes/probes were differentially up or down regulated between treatments. In intestinal tissue samples obtained on d 35 no differences in gene expression were observed. Probes of d 23 pw that were differently expressed and had an annotation were subsequently used as input for further functional analysis using DAVID and Gene Decks databases. The analysis did not result in the identification of gene sets that were differentially expressed between dietary treatments. However, it was shown that a number of upregulated genes in the jejunal mucosa on d 23 pw by the high zinc intervention are involved in pathways related to mineral absorption, immune signalling and cell energy metabolism (glycolysis and gluconeogenesis). A few down regulated genes by the Zn intervention are also involved in immune signalling pathways. It was concluded from the present study that provision of a diet with a high concentration of zinc as zinc oxide during a short period of time (9 days) to piglets in the post weaning period (d 14-23 pw) induces differences on the intestinal expression of genes in part related to the functioning of the local innate immune system. The high dietary zinc intervention can therefore be considered as a suitable model for studying relationships between dietary interventions and development of immune competence in post weaning piglets.

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Chemotherapy modulates intestinal immune gene expression in piglets including surfactant protein-D and DMBT1

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