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Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6
OBJECTIVE: We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds. METHODS: Mononuclear ce...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449041/ https://www.ncbi.nlm.nih.gov/pubmed/34302321 http://dx.doi.org/10.1002/acr2.11305 |
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author | Sun, Jitong Kumar Panda, Pritam Kumar Samal, Shailesh Ahuja, Rajeev Ajeganova, Sofia Hafström, Ingiäld Liu, Anquan Frostegård, Johan |
author_facet | Sun, Jitong Kumar Panda, Pritam Kumar Samal, Shailesh Ahuja, Rajeev Ajeganova, Sofia Hafström, Ingiäld Liu, Anquan Frostegård, Johan |
author_sort | Sun, Jitong |
collection | PubMed |
description | OBJECTIVE: We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds. METHODS: Mononuclear cells from 10 patients with SLE and 10 controls were cultured in conditions that induce Th17 and/or Treg cell polarization and/or apoptosis and were studied by FACScan. Gene expression was determined by quantitative real‐time reverse transcription–polymerase chain reaction. Cytokines in plasma were determined by enzyme‐linked immunosorbent assay. The Search Tool for Interactions of Chemicals (STITCH) was used to retrieve information regarding the binding properties of atorvastatin. RESULTS: Among patients with SLE, the proportion of Th17 (CD4(+)IL17(+)) cells was higher compared with controls after activation, with Th17 or Treg polarizing cytokines, phorbol myristate acetate, and ionomycin. In contrast, Treg cells (CD4(+)CD25(+)CD127(dim/−)) frequencies were lower. CD95 stimulation induced relatively more apoptosis in Treg cells and less in Th17 cells, as compared with controls. Addition of atorvastatin normalized Th17/Treg cell balance and apoptosis induction. Accordingly, the ratio of RORC/FoxP3 decreased in patients with SLE. Interleukin 17 and interleukin 6 (IL‐6) levels were increased in patients with SLE. Atorvastatin interacted strongly with C‐reactive protein (CRP) and also significantly with IL‐6. CONCLUSION: There is a higher proportion of Th17 cells and a lower proportion of Treg cells in patients with SLE after activation. Th17 cells were more resistant than Treg cells to CD95‐induced apoptosis in SLE. Atorvastatin normalized these effects. Our findings reveal a novel mechanism behind the imbalance of Th17/Treg cells with implications for treatment in SLE. We determine for the first time simulated interaction between atorvastatin, CRP, and IL‐6, implying a novel role of atorvastatin. |
format | Online Article Text |
id | pubmed-8449041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84490412021-12-21 Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 Sun, Jitong Kumar Panda, Pritam Kumar Samal, Shailesh Ahuja, Rajeev Ajeganova, Sofia Hafström, Ingiäld Liu, Anquan Frostegård, Johan ACR Open Rheumatol Original Articles OBJECTIVE: We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds. METHODS: Mononuclear cells from 10 patients with SLE and 10 controls were cultured in conditions that induce Th17 and/or Treg cell polarization and/or apoptosis and were studied by FACScan. Gene expression was determined by quantitative real‐time reverse transcription–polymerase chain reaction. Cytokines in plasma were determined by enzyme‐linked immunosorbent assay. The Search Tool for Interactions of Chemicals (STITCH) was used to retrieve information regarding the binding properties of atorvastatin. RESULTS: Among patients with SLE, the proportion of Th17 (CD4(+)IL17(+)) cells was higher compared with controls after activation, with Th17 or Treg polarizing cytokines, phorbol myristate acetate, and ionomycin. In contrast, Treg cells (CD4(+)CD25(+)CD127(dim/−)) frequencies were lower. CD95 stimulation induced relatively more apoptosis in Treg cells and less in Th17 cells, as compared with controls. Addition of atorvastatin normalized Th17/Treg cell balance and apoptosis induction. Accordingly, the ratio of RORC/FoxP3 decreased in patients with SLE. Interleukin 17 and interleukin 6 (IL‐6) levels were increased in patients with SLE. Atorvastatin interacted strongly with C‐reactive protein (CRP) and also significantly with IL‐6. CONCLUSION: There is a higher proportion of Th17 cells and a lower proportion of Treg cells in patients with SLE after activation. Th17 cells were more resistant than Treg cells to CD95‐induced apoptosis in SLE. Atorvastatin normalized these effects. Our findings reveal a novel mechanism behind the imbalance of Th17/Treg cells with implications for treatment in SLE. We determine for the first time simulated interaction between atorvastatin, CRP, and IL‐6, implying a novel role of atorvastatin. John Wiley and Sons Inc. 2021-07-23 /pmc/articles/PMC8449041/ /pubmed/34302321 http://dx.doi.org/10.1002/acr2.11305 Text en © 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Sun, Jitong Kumar Panda, Pritam Kumar Samal, Shailesh Ahuja, Rajeev Ajeganova, Sofia Hafström, Ingiäld Liu, Anquan Frostegård, Johan Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
title | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
title_full | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
title_fullStr | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
title_full_unstemmed | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
title_short | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
title_sort | effects of atorvastatin on t‐cell activation and apoptosis in systemic lupus erythematosus and novel simulated interactions with c‐reactive protein and interleukin 6 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449041/ https://www.ncbi.nlm.nih.gov/pubmed/34302321 http://dx.doi.org/10.1002/acr2.11305 |
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