Inhibition of Proteasome Activity Upregulates IL-6 Expression in RPE Cells through the Activation of P38 MAPKs
| العنوان: | Inhibition of Proteasome Activity Upregulates IL-6 Expression in RPE Cells through the Activation of P38 MAPKs |
|---|---|
| المؤلفون: | Tingyu Qin, Shasha Gao |
| المصدر: | Journal of Ophthalmology Journal of Ophthalmology, Vol 2018 (2018) |
| بيانات النشر: | Hindawi Limited, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Article Subject, p38 mitogen-activated protein kinases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, lcsh:Ophthalmology, Western blot, MG132, medicine, Retinal pigment epithelium, medicine.diagnostic_test, Kinase, business.industry, Molecular biology, Blot, Ophthalmology, 030104 developmental biology, medicine.anatomical_structure, chemistry, Proteasome, lcsh:RE1-994, 030221 ophthalmology & optometry, Proteasome inhibitor, business, Research Article, medicine.drug |
| الوصف: | Purpose. As far as we know, during the development of age-related macular degeneration (AMD), the activity of proteasome in retinal pigment epithelium cells (RPE) gradually decreases. And a lot of research has shown that age-related macular degeneration is closely related to inflammation and autoimmune. Moreover, there are many cytokines (CKs) involved in the course of inflammation. In this study, we are going to investigate how the decrease of proteasome activity affects the production of interleukin-6 (IL-6) in human retinal pigment epithelium cells (ARPE-19). Methods. Cultured ARPE-19 was treated with or without MG132, a proteasome inhibitor, and the levels of IL-6 mRNA (messenger ribonucleic acid) in RPE at 1 h, 4 h, 8 h, and IL-6 protein in the culture medium at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were measured by real-time polymerase chain reaction (real-time PCR) and enzyme-linked immunosorbent assay (ELISA). The protein levels of MCP-1 (monocyte chemoattractant protein-1) in the culture medium at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were also measured by ELISA. Then we tested which of cell signal pathways regulating the production of IL-6 were activated when we added MG132 into the medium by Western blot and electrophoretic mobility shift assays (EMSA). After that, we put the inhibitors of these activated cell signal pathways into the medium individually to see which inhibitor can counteract the effect of upregulating the levels of IL-6 in the culture medium of RPE. Results. MG132 decreased the secretion of MCP-1 in the culture medium of RPE, but it increased the expression of IL-6 mRNA in RPE and IL-6 protein level in the culture medium of RPE. MG132 treatment was also found to enhance the level of phosphorylated p38 mitogen-activated protein kinases (MAPKs) and c-Jun N-terminal Kinase (JNK) by Western blotting. More importantly, the effect of MG132 on upregulating the levels of IL-6 was inhibited by SB203580, an inhibitor of P38 MAP kinases. But the JNK inhibitor, SP600125, cannot prevent the effect of upregulating the levels of IL-6 by MG132 in the RPE culture medium. Conclusions. We concluded that the proteasome inhibitor, MG132, upregulates IL-6 production in RPE cells through the activation of P38 MAPKs. |
| وصف الملف: | text/xhtml |
| تدمد: | 2090-0058 2090-004X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b1b4199ca1b2629fb69555bb4c401c2Test https://doi.org/10.1155/2018/5392432Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2b1b4199ca1b2629fb69555bb4c401c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20900058 2090004X |
|---|