Cargando…
Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation
BACKGROUND: Immunotransmitters (e.g., neurotransmitters and neuromodulators) could orchestrate diverse immune responses; however, the elaborated mechanism by which melatonergic activation governs inflammation remains less defined. METHODS: Primary macrophages, various cell lines, and Pasteurella mul...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858632/ https://www.ncbi.nlm.nih.gov/pubmed/35184395 http://dx.doi.org/10.1002/ctm2.716 |
_version_ | 1784654281649946624 |
---|---|
author | Xia, Yaoyao Zhang, Qingzhuo Ye, Yuyi Wu, Xiaoyan He, Fang Peng, Yuanyi Yin, Yulong Ren, Wenkai |
author_facet | Xia, Yaoyao Zhang, Qingzhuo Ye, Yuyi Wu, Xiaoyan He, Fang Peng, Yuanyi Yin, Yulong Ren, Wenkai |
author_sort | Xia, Yaoyao |
collection | PubMed |
description | BACKGROUND: Immunotransmitters (e.g., neurotransmitters and neuromodulators) could orchestrate diverse immune responses; however, the elaborated mechanism by which melatonergic activation governs inflammation remains less defined. METHODS: Primary macrophages, various cell lines, and Pasteurella multocida (PmCQ2)‐infected mice were respectively used to illustrate the influence of melatonergic signalling on inflammation in vitro and in vivo. A series of methods (e.g., RNA‐seq, metabolomics, and genetic manipulation) were conducted to reveal the mechanism whereby melatonergic signalling reduces macrophage inflammation. RESULTS: Here, we demonstrate that melatonergic activation substantially lessens interleukin (IL)‐1β‐dependent inflammation. Treatment of macrophages with melatonin rewires metabolic program, as well as remodels signalling pathways which depends on interferon regulatory factor (IRF) 7. Mechanistically, melatonin acts via membrane receptor (MT) 1 to increase heat shock factor (Hsf) 1 expression through lowering the inactive glycogen synthase kinase (GSK3) β, thereby transcriptionally inhibiting interferon (IFN)‐γ receptor (IFNGR) 2 and ultimately causing defective canonical signalling events [Janus kinase (JAK) 1/2‐signal transducer and activator of transcription (STAT) 1‐IRF7] and lower IL‐1β production in macrophages. Moreover, we find that melatonin amplifies host protective responses to PmCQ2 infection‐induced pneumonia. CONCLUSIONS: Our conceptual framework provides potential therapeutic targets to prevent and/or treat inflammatory diseases associating with excessive IL‐1β production. |
format | Online Article Text |
id | pubmed-8858632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88586322022-03-31 Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation Xia, Yaoyao Zhang, Qingzhuo Ye, Yuyi Wu, Xiaoyan He, Fang Peng, Yuanyi Yin, Yulong Ren, Wenkai Clin Transl Med Research Articles BACKGROUND: Immunotransmitters (e.g., neurotransmitters and neuromodulators) could orchestrate diverse immune responses; however, the elaborated mechanism by which melatonergic activation governs inflammation remains less defined. METHODS: Primary macrophages, various cell lines, and Pasteurella multocida (PmCQ2)‐infected mice were respectively used to illustrate the influence of melatonergic signalling on inflammation in vitro and in vivo. A series of methods (e.g., RNA‐seq, metabolomics, and genetic manipulation) were conducted to reveal the mechanism whereby melatonergic signalling reduces macrophage inflammation. RESULTS: Here, we demonstrate that melatonergic activation substantially lessens interleukin (IL)‐1β‐dependent inflammation. Treatment of macrophages with melatonin rewires metabolic program, as well as remodels signalling pathways which depends on interferon regulatory factor (IRF) 7. Mechanistically, melatonin acts via membrane receptor (MT) 1 to increase heat shock factor (Hsf) 1 expression through lowering the inactive glycogen synthase kinase (GSK3) β, thereby transcriptionally inhibiting interferon (IFN)‐γ receptor (IFNGR) 2 and ultimately causing defective canonical signalling events [Janus kinase (JAK) 1/2‐signal transducer and activator of transcription (STAT) 1‐IRF7] and lower IL‐1β production in macrophages. Moreover, we find that melatonin amplifies host protective responses to PmCQ2 infection‐induced pneumonia. CONCLUSIONS: Our conceptual framework provides potential therapeutic targets to prevent and/or treat inflammatory diseases associating with excessive IL‐1β production. John Wiley and Sons Inc. 2022-02-20 /pmc/articles/PMC8858632/ /pubmed/35184395 http://dx.doi.org/10.1002/ctm2.716 Text en © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Xia, Yaoyao Zhang, Qingzhuo Ye, Yuyi Wu, Xiaoyan He, Fang Peng, Yuanyi Yin, Yulong Ren, Wenkai Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation |
title | Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation |
title_full | Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation |
title_fullStr | Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation |
title_full_unstemmed | Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation |
title_short | Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation |
title_sort | melatonergic signalling instructs transcriptional inhibition of ifngr2 to lessen interleukin‐1β‐dependent inflammation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858632/ https://www.ncbi.nlm.nih.gov/pubmed/35184395 http://dx.doi.org/10.1002/ctm2.716 |
work_keys_str_mv | AT xiayaoyao melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation AT zhangqingzhuo melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation AT yeyuyi melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation AT wuxiaoyan melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation AT hefang melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation AT pengyuanyi melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation AT yinyulong melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation AT renwenkai melatonergicsignallinginstructstranscriptionalinhibitionofifngr2tolesseninterleukin1bdependentinflammation |