ICAM-1 Abundance Is Increased in Pancreatic Islets of Hyperglycemic Female NOD Mice and Is Rapidly Upregulated by NF-κB in Pancreatic β-Cells
| العنوان: | ICAM-1 Abundance Is Increased in Pancreatic Islets of Hyperglycemic Female NOD Mice and Is Rapidly Upregulated by NF-κB in Pancreatic β-Cells |
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| المؤلفون: | Thomas M. Martin, Susan J. Burke, Heidi M. Batdorf, David H. Burk, Sujoy Ghosh, Samuel D. Dupuy, Michael D. Karlstad, J. Jason Collier |
| المصدر: | The Journal of Immunology. 209:569-581 |
| بيانات النشر: | The American Association of Immunologists, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Type 1 diabetes (T1D) is classified as an autoimmune disease where pancreatic β-cells are specifically targeted by cells of the immune system. The molecular mechanisms underlying this process are not completely understood. Herein, we identified that the Icam1 gene and ICAM-1 protein were selectively elevated in female NOD mice relative to male mice, fitting with the sexual dimorphism of diabetes onset in this key mouse model of T1D. In addition, ICAM-1 abundance was greater in hyperglycemic female NOD mice than in age-matched normoglycemic female NOD mice. Moreover, we discovered that the Icam1 gene was rapidly upregulated in response to IL-1β in mouse, rat, and human islets and in 832/13 rat insulinoma cells. This early temporal genetic regulation requires key components of the NF-κB pathway and was associated with rapid recruitment of the p65 transcriptional subunit of NF-κB to corresponding κB elements within the Icam1 gene promoter. In addition, RNA polymerase II recruitment to the Icam1 gene promoter in response to IL-1β was consistent with p65 occupancy at κB elements, histone chemical modifications, and increased mRNA abundance. Thus, we conclude that β-cells undergo rapid genetic reprogramming by IL-1β to enhance expression of the Icam1 gene and that elevations in ICAM-1 are associated with hyperglycemia in NOD mice. These findings are highly relevant to, and highlight the importance of, pancreatic β-cell communication with the immune system. Collectively, these observations reveal a portion of the complex molecular events associated with onset and progression of T1D. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::100bc265a6919ee9f002d92bcad35f18 https://doi.org/10.4049/jimmunol.2200065 |
| رقم الأكسشن: | edsair.doi.dedup.....100bc265a6919ee9f002d92bcad35f18 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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