Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon.
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 associat...
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| _version_ | 1849766171161657344 |
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| author | Vanesa Stojanovska Rachel M McQuade Sarah Fraser Monica Prakash Shakuntla Gondalia Rhian Stavely Enzo Palombo Vasso Apostolopoulos Samy Sakkal Kulmira Nurgali |
| author_facet | Vanesa Stojanovska Rachel M McQuade Sarah Fraser Monica Prakash Shakuntla Gondalia Rhian Stavely Enzo Palombo Vasso Apostolopoulos Samy Sakkal Kulmira Nurgali |
| author_sort | Vanesa Stojanovska |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-3e0a45eb421144e59c72d9d01bd85bb6 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3e0a45eb421144e59c72d9d01bd85bb62025-08-20T03:04:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019835910.1371/journal.pone.0198359Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon.Vanesa StojanovskaRachel M McQuadeSarah FraserMonica PrakashShakuntla GondaliaRhian StavelyEnzo PalomboVasso ApostolopoulosSamy SakkalKulmira NurgaliOxaliplatin 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.https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198359/1/pone.0198359.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210218%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210218T134720Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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 |
| spellingShingle | Vanesa Stojanovska Rachel M McQuade Sarah Fraser Monica Prakash Shakuntla Gondalia Rhian Stavely Enzo Palombo Vasso Apostolopoulos Samy Sakkal Kulmira Nurgali Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. PLoS ONE |
| title | Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. |
| title_full | Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. |
| title_fullStr | Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. |
| title_full_unstemmed | Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. |
| title_short | Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. |
| title_sort | oxaliplatin induced changes in microbiota tlr4 cells and enhanced hmgb1 expression in the murine colon |
| url | https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198359/1/pone.0198359.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210218%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210218T134720Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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 |
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