Cargando…
The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress
BACKGROUND: Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to th...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568525/ https://www.ncbi.nlm.nih.gov/pubmed/34745423 http://dx.doi.org/10.1155/2021/7617839 |
_version_ | 1784594459060600832 |
---|---|
author | Tian, Jun Wang, Yaojun Ding, Ming Zhang, Yue Chi, Jiaoni Wang, Tao Jiao, Bin Jian, Zhe Yi, Xiuli Huang, Ye Liu, Ling Li, Kai Chen, Jiaxi Wang, Gang Gao, Tianwen Li, Chunying Li, Qiang |
author_facet | Tian, Jun Wang, Yaojun Ding, Ming Zhang, Yue Chi, Jiaoni Wang, Tao Jiao, Bin Jian, Zhe Yi, Xiuli Huang, Ye Liu, Ling Li, Kai Chen, Jiaxi Wang, Gang Gao, Tianwen Li, Chunying Li, Qiang |
author_sort | Tian, Jun |
collection | PubMed |
description | BACKGROUND: Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to the extracellular environment are still unclear. Apoptotic bodies (ABs) have always been considered as a key source of immunomodulators and autoantigens. Yet, the role of ABs in the immune mechanism of vitiligo is still unknown. PURPOSE: To explore whether MC's autoantigens translocate into ABs during oxidative stress-induced apoptosis and study the molecular mechanisms underlying autoantigen migration and AB formation. METHODS: PIG3V (an immortalized human vitiligo melanocyte cell line) were treated with H(2)O(2), and ABs were separated. Transmission electron microscopy, flow cytometry, Western blot, mass spectrometry, and other methods were used to determine the relocation of specific antigens in PIG3V cells to ABs. After pretreatment with specific inhibitors (Rho kinase (Y-27632), myosin light chain kinase (MLCK, ML-9), pan-caspase (zVAD-FMK), and JNK (SP600125)), the pathway of autoantigen translocation into ABs and the formation of apoptotic bodies were determined. RESULTS: When treated with 0.8 mM H(2)O(2), ABs were released from these cells. Autoantigens such as tyrosinase-related protein 1 (TYRP-1) and cleavage nuclear membrane antigen Lamin A/C (Asp230) were concentrated in ABs. The expression of autoantigens and the formation of ABs increased in a time- and dose-dependent manner after treatment with H(2)O(2), while the application of specific inhibitors inhibited the formation of apoptotic bodies, i.e., the expression of antigens. CONCLUSION: Vitiligo autoantigens translocate into ABs in the process of apoptosis induced by oxidative stress. The cytoskeletal protein activation pathway and the JNK-related apoptosis pathway are involved in the transport of autoantigens and the formation of ABs. ABs may be the key bridge between MC cell apoptosis and cellular immunity. |
format | Online Article Text |
id | pubmed-8568525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-85685252021-11-05 The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress Tian, Jun Wang, Yaojun Ding, Ming Zhang, Yue Chi, Jiaoni Wang, Tao Jiao, Bin Jian, Zhe Yi, Xiuli Huang, Ye Liu, Ling Li, Kai Chen, Jiaxi Wang, Gang Gao, Tianwen Li, Chunying Li, Qiang Oxid Med Cell Longev Research Article BACKGROUND: Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to the extracellular environment are still unclear. Apoptotic bodies (ABs) have always been considered as a key source of immunomodulators and autoantigens. Yet, the role of ABs in the immune mechanism of vitiligo is still unknown. PURPOSE: To explore whether MC's autoantigens translocate into ABs during oxidative stress-induced apoptosis and study the molecular mechanisms underlying autoantigen migration and AB formation. METHODS: PIG3V (an immortalized human vitiligo melanocyte cell line) were treated with H(2)O(2), and ABs were separated. Transmission electron microscopy, flow cytometry, Western blot, mass spectrometry, and other methods were used to determine the relocation of specific antigens in PIG3V cells to ABs. After pretreatment with specific inhibitors (Rho kinase (Y-27632), myosin light chain kinase (MLCK, ML-9), pan-caspase (zVAD-FMK), and JNK (SP600125)), the pathway of autoantigen translocation into ABs and the formation of apoptotic bodies were determined. RESULTS: When treated with 0.8 mM H(2)O(2), ABs were released from these cells. Autoantigens such as tyrosinase-related protein 1 (TYRP-1) and cleavage nuclear membrane antigen Lamin A/C (Asp230) were concentrated in ABs. The expression of autoantigens and the formation of ABs increased in a time- and dose-dependent manner after treatment with H(2)O(2), while the application of specific inhibitors inhibited the formation of apoptotic bodies, i.e., the expression of antigens. CONCLUSION: Vitiligo autoantigens translocate into ABs in the process of apoptosis induced by oxidative stress. The cytoskeletal protein activation pathway and the JNK-related apoptosis pathway are involved in the transport of autoantigens and the formation of ABs. ABs may be the key bridge between MC cell apoptosis and cellular immunity. Hindawi 2021-10-28 /pmc/articles/PMC8568525/ /pubmed/34745423 http://dx.doi.org/10.1155/2021/7617839 Text en Copyright © 2021 Jun Tian et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Tian, Jun Wang, Yaojun Ding, Ming Zhang, Yue Chi, Jiaoni Wang, Tao Jiao, Bin Jian, Zhe Yi, Xiuli Huang, Ye Liu, Ling Li, Kai Chen, Jiaxi Wang, Gang Gao, Tianwen Li, Chunying Li, Qiang The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress |
title | The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress |
title_full | The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress |
title_fullStr | The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress |
title_full_unstemmed | The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress |
title_short | The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress |
title_sort | formation of melanocyte apoptotic bodies in vitiligo and the relocation of vitiligo autoantigens under oxidative stress |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568525/ https://www.ncbi.nlm.nih.gov/pubmed/34745423 http://dx.doi.org/10.1155/2021/7617839 |
work_keys_str_mv | AT tianjun theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT wangyaojun theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT dingming theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT zhangyue theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT chijiaoni theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT wangtao theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT jiaobin theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT jianzhe theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT yixiuli theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT huangye theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT liuling theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT likai theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT chenjiaxi theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT wanggang theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT gaotianwen theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT lichunying theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT liqiang theformationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT tianjun formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT wangyaojun formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT dingming formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT zhangyue formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT chijiaoni formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT wangtao formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT jiaobin formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT jianzhe formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT yixiuli formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT huangye formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT liuling formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT likai formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT chenjiaxi formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT wanggang formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT gaotianwen formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT lichunying formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress AT liqiang formationofmelanocyteapoptoticbodiesinvitiligoandtherelocationofvitiligoautoantigensunderoxidativestress |