Early IL-5 transgenesis of colitis-associated colorectal cancer (CA-CRC) mouse model exacerbate the disease severity

Abstract

Aims: To explore the role of IL-5 in eosinophils induction and cytokine modulation on the development of colitis-associated colorectal cancer mouse model (CA-CRC).
Methods and Material: A plasmid carrying the mouse IL-5 gene (IL-5 transgenesis) was injected to the mice with concurrently induction of CA-CRC mouse model, Then (CA-CRC) development, cytokine gene expression, cell dynamics in tumor vicinity and peritoneal cavity were analysed.
Results: A protumorigenic role of IL-5 was shown on early stages of CRC development as mice experienced severe physical symptoms including: rectal bleeding, diarrhea and significant reduction in body weight gain. Late findings of IL-5 transgenesis revealed higher tumor rates (89.0% vs 50%), significantly higher tumor count (15.1±7.2 vs 7.3±10.6 per colon), higher average tumor size (9.1±5.2 vs 4.4±6.5 mm), higher invasiveness index and shorter colon length. Microscopic examination of tumors revealed the presence of higher plasma cell count but lower eosinophils in AOM-DSS-pIL-5 treated group when compared to AOM-DSS group. Cytokine gene expression pointed out to the downregulation of IL-10 and TGF-β and the overexpression of IFN-γ in both tumor bearing groups compared to pIL-5 group. IL-5 treatment of AOM-DSS mice resulted in insignificant reduction in IL-5 gene expression in colon tissue that was associated with lower eosinophil count in the peritoneal cavity wash.
Conclusions: Immunomodulatory effect of early IL-5 expression in the CA-CRC and its role in the early migration of eosinophils to colon epithelia during colitis development raised the colitis severity and induced higher polyp rate formation and consequently higher tumor load.

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