Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol
Deoxynivalenol (DON), a prevalent mycotoxin produced by Fusarium species, contaminates global agricultural products and poses significant health risks, particularly to the gastrointestinal (GI) system. DON exposure disrupts ribosomal function, inducing stress responses linked to various inflammatory...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324017214 |
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| author | Juil Kim BoGyoung Song Ki-Hyung Kim Yuseok Moon |
| author_facet | Juil Kim BoGyoung Song Ki-Hyung Kim Yuseok Moon |
| author_sort | Juil Kim |
| collection | DOAJ |
| description | Deoxynivalenol (DON), a prevalent mycotoxin produced by Fusarium species, contaminates global agricultural products and poses significant health risks, particularly to the gastrointestinal (GI) system. DON exposure disrupts ribosomal function, inducing stress responses linked to various inflammatory diseases, including inflammatory bowel disease (IBD). In this study, we elucidate a novel regulatory mechanism involving ribosomal proteins (RPs) RPL13A and RPS3, which mediate proinflammatory chemokine production in DON-exposed gut epithelial cells. Through a combination of transcriptomic analysis and experimental models, we demonstrate that while RPL13A negatively regulates inflammation by enhancing the anti-inflammatory transcription factor ATF3, RPS3 acts as a proinflammatory driver, promoting chemokine production via activation of MAPK pathways, transcriptional upregulation of EGR-1, and stabilization of mRNA through cytosolic translocation of HuR. Our findings reveal a dynamic interplay between RPL13A and RPS3, wherein RPL13A counteracts the proinflammatory effects of RPS3, offering a finely tuned regulatory axis in the inflammatory response to environmental toxins. These insights provide potential molecular targets for therapeutic intervention in toxin-induced inflammatory diseases of the gut, highlighting the non-canonical roles of ribosomal proteins in modulating immune responses to environmental stressors. |
| format | Article |
| id | doaj-art-f77be48f804d4824a7eb3a6e7ee160bf |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-f77be48f804d4824a7eb3a6e7ee160bf2025-01-23T05:25:57ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117645Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenolJuil Kim0BoGyoung Song1Ki-Hyung Kim2Yuseok Moon3Laboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences, Pusan National University, Yangsan, Republic of Korea; Department of Obstetrics and Gynecology, College of Medicine, Pusan National University, Pusan National University, Busan, Republic of Korea; Program of Total Foodtech and PNU-Korea Maritime Institute (KMI) Collaborative Research Center, Busan, Republic of KoreaLaboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences, Pusan National University, Yangsan, Republic of KoreaDepartment of Obstetrics and Gynecology, College of Medicine, Pusan National University, Pusan National University, Busan, Republic of Korea; Biomedical Research Institute, Pusan National University, Busan, Republic of KoreaLaboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences, Pusan National University, Yangsan, Republic of Korea; Biomedical Research Institute, Pusan National University, Busan, Republic of Korea; Graduate Program of Genomic Data Sciences, Pusan National University, Yangsan, Republic of Korea; Program of Total Foodtech and PNU-Korea Maritime Institute (KMI) Collaborative Research Center, Busan, Republic of Korea; Correspondence to: Department of Integrative Biomedical Sciences, Pusan National University, Yangsan 50612, Republic of Korea.Deoxynivalenol (DON), a prevalent mycotoxin produced by Fusarium species, contaminates global agricultural products and poses significant health risks, particularly to the gastrointestinal (GI) system. DON exposure disrupts ribosomal function, inducing stress responses linked to various inflammatory diseases, including inflammatory bowel disease (IBD). In this study, we elucidate a novel regulatory mechanism involving ribosomal proteins (RPs) RPL13A and RPS3, which mediate proinflammatory chemokine production in DON-exposed gut epithelial cells. Through a combination of transcriptomic analysis and experimental models, we demonstrate that while RPL13A negatively regulates inflammation by enhancing the anti-inflammatory transcription factor ATF3, RPS3 acts as a proinflammatory driver, promoting chemokine production via activation of MAPK pathways, transcriptional upregulation of EGR-1, and stabilization of mRNA through cytosolic translocation of HuR. Our findings reveal a dynamic interplay between RPL13A and RPS3, wherein RPL13A counteracts the proinflammatory effects of RPS3, offering a finely tuned regulatory axis in the inflammatory response to environmental toxins. These insights provide potential molecular targets for therapeutic intervention in toxin-induced inflammatory diseases of the gut, highlighting the non-canonical roles of ribosomal proteins in modulating immune responses to environmental stressors.http://www.sciencedirect.com/science/article/pii/S0147651324017214DeoxynivalenolRibosomal proteinsGut epithelial cellsProinflammatory chemokinesRibotoxic stress response |
| spellingShingle | Juil Kim BoGyoung Song Ki-Hyung Kim Yuseok Moon Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol Ecotoxicology and Environmental Safety Deoxynivalenol Ribosomal proteins Gut epithelial cells Proinflammatory chemokines Ribotoxic stress response |
| title | Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol |
| title_full | Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol |
| title_fullStr | Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol |
| title_full_unstemmed | Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol |
| title_short | Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol |
| title_sort | ribosomal proteins mediate non canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol |
| topic | Deoxynivalenol Ribosomal proteins Gut epithelial cells Proinflammatory chemokines Ribotoxic stress response |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324017214 |
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