HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signaling
Abstract Introduction Allergic rhinitis (AR) is frequently known as a chronic respiratory disease with a global high prevalence. The pivotal roles of histone deacetylase 4 (HDAC4) in multiple human diseases have been underlined by numerous studies. Nevertheless, whether HDAC4 is implicated in AR rem...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.692 |
| _version_ | 1797989874478874624 |
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| author | Hangyu Xu Lingjun Wang Huaqun Chen Hefei Cai |
| author_facet | Hangyu Xu Lingjun Wang Huaqun Chen Hefei Cai |
| author_sort | Hangyu Xu |
| collection | DOAJ |
| description | Abstract Introduction Allergic rhinitis (AR) is frequently known as a chronic respiratory disease with a global high prevalence. The pivotal roles of histone deacetylase 4 (HDAC4) in multiple human diseases have been underlined by numerous studies. Nevertheless, whether HDAC4 is implicated in AR remains to be elaborated. The objective of the current study is to clarify the impacts of HDAC4 on AR. Methods First, human nasal epithelial cells (hNECs) were pretreated by interleukin‐13 (IL‐13). HDAC4 expression in hNECs with the presence or absence of IL‐13 treatment was tested by quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) and western blot. Following, after HDAC4 was depleted, levels of histamine, Immunoglobulin E (IgE) and inflammatory factors were analyzed by ELISA assay. Then, Mucin‐5AC (MUC5AC) expression was examined through RT‐qPCR, western blot, and IF assay. Western blot was to analyze the expression of sirtuin 1 (SIRT1)/nuclear factor‐kappaB (NF‐κB) signaling‐related proteins. After IL‐13‐induced hNECs were cotransfected with HDAC4 interference plasmids and SIRT1 inhibitor EX527, the functional experiments above were conducted again. Results The experimental data in this study presented that HDAC4 expression was increased in IL‐13‐induced hNECs. Silencing of HDAC4 cut down the levels of histamine, IgE and inflammatory factors and the expression of MUC5AC. Additionally, knockdown of HDAC4 led to the activation of SIRT1/NF‐κB signaling. Further, the downregulated levels of histamine, IgE and inflammatory factors and the expression of MUC5AC imposed by HDAC4 interference were all reversed by EX527. Conclusions In short, HDAC4 inhibition activated SIRT1/NF‐κB signaling to mitigate inflammatory response and mucus production in IL‐13‐treated nasal epithelial cells in AR. |
| first_indexed | 2024-04-11T08:27:31Z |
| format | Article |
| id | doaj.art-12447e05d7ad4a5d808147b1f46d24af |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-04-11T08:27:31Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-12447e05d7ad4a5d808147b1f46d24af2022-12-22T04:34:40ZengWileyImmunity, Inflammation and Disease2050-45272022-11-011011n/an/a10.1002/iid3.692HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signalingHangyu Xu0Lingjun Wang1Huaqun Chen2Hefei Cai3Department of Otolaryngology, Taizhou Central Hospital Taizhou University Hospital Taizhou Zhejiang ChinaDepartment of General Practice, Taizhou Central Hospital Taizhou University Hospital Taizhou Zhejiang ChinaDepartment of Geriatrics, Taizhou Central Hospital Taizhou University Hospital Taizhou Zhejiang ChinaDepartment of Pediatrics, Taizhou Central Hospital Taizhou University Hospital Taizhou Zhejiang ChinaAbstract Introduction Allergic rhinitis (AR) is frequently known as a chronic respiratory disease with a global high prevalence. The pivotal roles of histone deacetylase 4 (HDAC4) in multiple human diseases have been underlined by numerous studies. Nevertheless, whether HDAC4 is implicated in AR remains to be elaborated. The objective of the current study is to clarify the impacts of HDAC4 on AR. Methods First, human nasal epithelial cells (hNECs) were pretreated by interleukin‐13 (IL‐13). HDAC4 expression in hNECs with the presence or absence of IL‐13 treatment was tested by quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) and western blot. Following, after HDAC4 was depleted, levels of histamine, Immunoglobulin E (IgE) and inflammatory factors were analyzed by ELISA assay. Then, Mucin‐5AC (MUC5AC) expression was examined through RT‐qPCR, western blot, and IF assay. Western blot was to analyze the expression of sirtuin 1 (SIRT1)/nuclear factor‐kappaB (NF‐κB) signaling‐related proteins. After IL‐13‐induced hNECs were cotransfected with HDAC4 interference plasmids and SIRT1 inhibitor EX527, the functional experiments above were conducted again. Results The experimental data in this study presented that HDAC4 expression was increased in IL‐13‐induced hNECs. Silencing of HDAC4 cut down the levels of histamine, IgE and inflammatory factors and the expression of MUC5AC. Additionally, knockdown of HDAC4 led to the activation of SIRT1/NF‐κB signaling. Further, the downregulated levels of histamine, IgE and inflammatory factors and the expression of MUC5AC imposed by HDAC4 interference were all reversed by EX527. Conclusions In short, HDAC4 inhibition activated SIRT1/NF‐κB signaling to mitigate inflammatory response and mucus production in IL‐13‐treated nasal epithelial cells in AR.https://doi.org/10.1002/iid3.692allergic rhinitisHDAC4inflammatory responseMUC5ACSIRT1/NF‐κB signaling |
| spellingShingle | Hangyu Xu Lingjun Wang Huaqun Chen Hefei Cai HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signaling Immunity, Inflammation and Disease allergic rhinitis HDAC4 inflammatory response MUC5AC SIRT1/NF‐κB signaling |
| title | HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signaling |
| title_full | HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signaling |
| title_fullStr | HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signaling |
| title_full_unstemmed | HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signaling |
| title_short | HDAC4 depletion ameliorates IL‐13‐triggered inflammatory response and mucus production in nasal epithelial cells via activation of SIRT1/NF‐κB signaling |
| title_sort | hdac4 depletion ameliorates il 13 triggered inflammatory response and mucus production in nasal epithelial cells via activation of sirt1 nf κb signaling |
| topic | allergic rhinitis HDAC4 inflammatory response MUC5AC SIRT1/NF‐κB signaling |
| url | https://doi.org/10.1002/iid3.692 |
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