Chemotherapy Modulates Intestinal Immune Gene Expression Including Surfactant Protein-D and Deleted in Malignant Brain Tumors 1 in Piglets

Chemotherapy. 2016;61(4):204-16. doi: 10.1159/000442938. Epub 2016 Feb 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Busulfan / pharmacology
  • Busulfan / therapeutic use
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use
  • Disease Models, Animal
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Therapy, Combination
  • Gene Expression Regulation / drug effects
  • Immunity, Innate
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism
  • Mucositis / metabolism
  • Mucositis / pathology
  • Pulmonary Surfactant-Associated Protein D / deficiency
  • Pulmonary Surfactant-Associated Protein D / genetics
  • Pulmonary Surfactant-Associated Protein D / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Swine

Substances

  • Antineoplastic Agents
  • Pulmonary Surfactant-Associated Protein D
  • Doxorubicin
  • Cyclophosphamide
  • Busulfan