Chemotherapy modulates intestinal immune gene expression including surfactant Protein-D and deleted in malignant brain tumors 1 in piglets

Mathias Rathe*, Mads Thomassen, René L. Shen, Peter E.L. Pontoppidan, Steffen Husby, Klaus Müller, Torben A Kruse, Per T. Sangild

*Corresponding author for this work
7 Citations (Scopus)

Abstract

Background: Information about chemotherapy-induced intestinal gene expression may provide insight into the mechanisms underlying gut toxicity and help identify biomarkers and targets for intervention. Methods: We analyzed jejunal tissue from piglets subjected to two different, clinically relevant chemotherapy regimens: (1) busulfan plus cyclophosphamide (BUCY) and (2) doxorubicin (DOX). Results: Gene expression analysis identified 1,328 differentially expressed genes in the BUCY piglets and 594 in the DOX piglets, compared to controls. Similar changes in expression were found for 137 genes across the BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among the upregulated genes for both treatments. Conclusion: In the developing intestine, chemotherapy increases the expression of genes related to innate immune functions involved in surveillance, protection, and homeostasis of mucosal surfaces.

Original languageEnglish
JournalChemotherapy
Volume61
Issue number4
Pages (from-to)204-216
Number of pages13
ISSN0009-3157
DOIs
Publication statusPublished - 2016

Keywords

  • Chemotherapy-induced mucositis
  • Deleted in malignant brain tumors 1
  • Gastrointestinal toxicity
  • Mucosal barrier injury
  • Mucositis
  • Peptidoglycan recognition protein 2
  • Pig model
  • Surfactant protein-D

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