Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells
Interleukin-6 (IL-6) overproduction has been considered to contribute to inflammatory damage of glomerular mesangial cells (GMCs) in human mesangial proliferative glomerulonephritis (MsPGN) and its rat model called Thy-1 nephritis (Thy-1N). However, the regulatory mechanisms of IL-6 expression in GM...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.779667/full |
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| author | Lu Xia Yu Liu Zhiwei Zhang Yajuan Gong Tianyi Yu Dan Zhao Wen Qiu Yingwei Wang Jing Zhang Jing Zhang Jing Zhang |
| author_facet | Lu Xia Yu Liu Zhiwei Zhang Yajuan Gong Tianyi Yu Dan Zhao Wen Qiu Yingwei Wang Jing Zhang Jing Zhang Jing Zhang |
| author_sort | Lu Xia |
| collection | DOAJ |
| description | Interleukin-6 (IL-6) overproduction has been considered to contribute to inflammatory damage of glomerular mesangial cells (GMCs) in human mesangial proliferative glomerulonephritis (MsPGN) and its rat model called Thy-1 nephritis (Thy-1N). However, the regulatory mechanisms of IL-6 expression in GMCs upon sublytic C5b-9 timulation remain poorly understood. We found that Krüppel-like factor 4 (KLF4) bound to the IL-6 promoter (−618 to −126 nt) and activated IL-6 gene transcription. Furthermore, lysine residue 224 of KLF4 was acetylated by p300/CBP-associated factor (PCAF), which was important for KLF4-mediated transactivation. Moreover, lysine residue 5 on histone H2B and lysine residue 9 on histone H3 at the IL-6 promoter were also acetylated by PCAF, which resulted in an increase in IL-6 transcription. Besides, NF-κB activation promoted IL-6 expression by elevating the expression of PCAF. Overall, these findings suggest that sublytic C5b-9-induced the expression of IL-6 involves KLF4-mediated transactivation, PCAF-mediated acetylation of KLF4 and histones, and NF-κB activation in GMCs. |
| first_indexed | 2024-12-22T20:10:20Z |
| format | Article |
| id | doaj.art-538ed96dadc6424384a1fbee4d70aaa6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T20:10:20Z |
| publishDate | 2022-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-538ed96dadc6424384a1fbee4d70aaa62022-12-21T18:14:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.779667779667Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial CellsLu Xia0Yu Liu1Zhiwei Zhang2Yajuan Gong3Tianyi Yu4Dan Zhao5Wen Qiu6Yingwei Wang7Jing Zhang8Jing Zhang9Jing Zhang10Department of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Microbiology and Immunology, Jiangsu Health Vocational College, Nanjing, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Immunological Environment and Disease, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Antibody Technology of Ministry of Health, Nanjing Medical University, Nanjing, ChinaInterleukin-6 (IL-6) overproduction has been considered to contribute to inflammatory damage of glomerular mesangial cells (GMCs) in human mesangial proliferative glomerulonephritis (MsPGN) and its rat model called Thy-1 nephritis (Thy-1N). However, the regulatory mechanisms of IL-6 expression in GMCs upon sublytic C5b-9 timulation remain poorly understood. We found that Krüppel-like factor 4 (KLF4) bound to the IL-6 promoter (−618 to −126 nt) and activated IL-6 gene transcription. Furthermore, lysine residue 224 of KLF4 was acetylated by p300/CBP-associated factor (PCAF), which was important for KLF4-mediated transactivation. Moreover, lysine residue 5 on histone H2B and lysine residue 9 on histone H3 at the IL-6 promoter were also acetylated by PCAF, which resulted in an increase in IL-6 transcription. Besides, NF-κB activation promoted IL-6 expression by elevating the expression of PCAF. Overall, these findings suggest that sublytic C5b-9-induced the expression of IL-6 involves KLF4-mediated transactivation, PCAF-mediated acetylation of KLF4 and histones, and NF-κB activation in GMCs.https://www.frontiersin.org/articles/10.3389/fimmu.2021.779667/fullacetylationKLF4PCAFsublytic C5b-9IL-6 |
| spellingShingle | Lu Xia Yu Liu Zhiwei Zhang Yajuan Gong Tianyi Yu Dan Zhao Wen Qiu Yingwei Wang Jing Zhang Jing Zhang Jing Zhang Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells Frontiers in Immunology acetylation KLF4 PCAF sublytic C5b-9 IL-6 |
| title | Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells |
| title_full | Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells |
| title_fullStr | Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells |
| title_full_unstemmed | Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells |
| title_short | Modulation of IL-6 Expression by KLF4-Mediated Transactivation and PCAF-Mediated Acetylation in Sublytic C5b-9-Induced Rat Glomerular Mesangial Cells |
| title_sort | modulation of il 6 expression by klf4 mediated transactivation and pcaf mediated acetylation in sublytic c5b 9 induced rat glomerular mesangial cells |
| topic | acetylation KLF4 PCAF sublytic C5b-9 IL-6 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.779667/full |
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