Brief description
Oxaliplatin is a platinum-based chemotherapeutic used for cancer treatment. Its use associates with peripheral neuropathies and chronic gastrointestinal side-effects. Oxaliplatin induces immunogenic cell death by provoking the presentation of damage associated molecular patterns. The damage associated molecular patterns high-mobility group box 1 (HMGB1) protein exerts pro-inflammatory cytokine-like activity and binds to toll-like receptors (namely TLR4). Gastrointestinal microbiota may influence chemotherapeutic efficacy and contribute to local and systemic inflammation. We studied effects of oxaliplatin treatment on 1) TLR4 and high-mobility group box 1 expression within the colon; 2) gastrointestinal microbiota composition; 3) inflammation within the colon; 4) changes in Peyer’s patches and mesenteric lymph nodes immune populations in mice. TLR4+ cells displayed pseudopodia-like extensions characteristic of antigen sampling co-localised with high-mobility group box 1 -overexpressing cells in the colonic lamina propria from oxaliplatin-treated animals. Oxaliplatin treatment caused significant reduction in Parabacteroides and Prevotella1, but increase in Prevotella2 and Odoribacter bacteria at the genus level. Downregulation of pro-inflammatory cytokines and chemokines in colon samples, a reduction in macrophages and dendritic cells in mesenteric lymph nodes were found after oxaliplatin treatment. In conclusion, oxaliplatin treatment caused morphological changes in TLR4+ cells, increase in gram-negative microbiota and enhanced HMGB1 expression associated with immunosuppression in the colon.
Created: 12 06 2018
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- DOI : https://doi.org/10.1371/journal.pone.0198359.s001
- DOI : https://doi.org/10.1371/journal.pone.0198359.s002
- DOI : https://doi.org/10.1371/journal.pone.0198359.s003
- DOI : https://doi.org/10.1371/journal.pone.0198359.s004
- DOI : https://doi.org/10.1371/journal.pone.0198359.s005
- DOI : https://doi.org/10.1371/journal.pone.0198359.s006
- PURL : https://figshare.com/articles/Oxaliplatin-induced_changes_in_microbiota_TLR4_cells_and_enhanced_HMGB1_expression_in_the_murine_colon/6494246
- DOI : https://doi.org/10.1371/journal.pone.0198359
