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Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment
Fibroblasts are stromal cells abundant throughout tissues, including the lungs. Fibroblasts are integral coordinators of immune cell recruitment through chemokine secretion. Circadian rhythms direct the recruitment of immune cells to the lung, which in turn impacts response to infection and survival...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107448/ https://www.ncbi.nlm.nih.gov/pubmed/36624683 http://dx.doi.org/10.1096/fj.202201456R |
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author | Cox, Shannon L. O'Siorain, James R. He, Yan Lordan, Ronan Naik, Amruta Tang, Soon Yew Sengupta, Shaon FitzGerald, Garret A. Carroll, Richard G. Curtis, Annie M. |
author_facet | Cox, Shannon L. O'Siorain, James R. He, Yan Lordan, Ronan Naik, Amruta Tang, Soon Yew Sengupta, Shaon FitzGerald, Garret A. Carroll, Richard G. Curtis, Annie M. |
author_sort | Cox, Shannon L. |
collection | PubMed |
description | Fibroblasts are stromal cells abundant throughout tissues, including the lungs. Fibroblasts are integral coordinators of immune cell recruitment through chemokine secretion. Circadian rhythms direct the recruitment of immune cells to the lung, which in turn impacts response to infection and survival. Although fibroblasts display robust circadian rhythms, the contribution of the fibroblast molecular clock to lung‐specific migration of immune cells and recruitment remains to be established. Mice challenged intranasally with lipopolysaccharide (LPS) at dusk showed increased expression of the pro‐inflammatory cytokine IL‐1β and chemokine CXCL5 in the lung, which was accompanied by increased neutrophil recruitment. Primary lung fibroblasts with knockdown of the core clock gene Bmal1 and immortalized Bmal1 (−/−) lung fibroblasts also displayed increased Cxcl5 expression under IL‐1β stimulation. Conditioned media obtained from IL‐1β‐stimulated Bmal1 (−/−) immortalized fibroblasts‐induced greater neutrophil migration compared with Bmal1 (+/+) lung fibroblast controls. Phosphorylation of the NF‐κB subunit, p65, was enhanced in IL‐1β‐stimulated Bmal1 (−/−) lung fibroblasts, and pharmacological inhibition of NF‐κB attenuated the enhanced CXCL5 production and neutrophil recruitment observed in these cells. Collectively, these results demonstrate that Bmal1 represses NF‐κB activity in lung fibroblasts to control chemokine expression and immune cell recruitment during an inflammatory response. |
format | Online Article Text |
id | pubmed-10107448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101074482023-04-18 Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment Cox, Shannon L. O'Siorain, James R. He, Yan Lordan, Ronan Naik, Amruta Tang, Soon Yew Sengupta, Shaon FitzGerald, Garret A. Carroll, Richard G. Curtis, Annie M. FASEB J Research Articles Fibroblasts are stromal cells abundant throughout tissues, including the lungs. Fibroblasts are integral coordinators of immune cell recruitment through chemokine secretion. Circadian rhythms direct the recruitment of immune cells to the lung, which in turn impacts response to infection and survival. Although fibroblasts display robust circadian rhythms, the contribution of the fibroblast molecular clock to lung‐specific migration of immune cells and recruitment remains to be established. Mice challenged intranasally with lipopolysaccharide (LPS) at dusk showed increased expression of the pro‐inflammatory cytokine IL‐1β and chemokine CXCL5 in the lung, which was accompanied by increased neutrophil recruitment. Primary lung fibroblasts with knockdown of the core clock gene Bmal1 and immortalized Bmal1 (−/−) lung fibroblasts also displayed increased Cxcl5 expression under IL‐1β stimulation. Conditioned media obtained from IL‐1β‐stimulated Bmal1 (−/−) immortalized fibroblasts‐induced greater neutrophil migration compared with Bmal1 (+/+) lung fibroblast controls. Phosphorylation of the NF‐κB subunit, p65, was enhanced in IL‐1β‐stimulated Bmal1 (−/−) lung fibroblasts, and pharmacological inhibition of NF‐κB attenuated the enhanced CXCL5 production and neutrophil recruitment observed in these cells. Collectively, these results demonstrate that Bmal1 represses NF‐κB activity in lung fibroblasts to control chemokine expression and immune cell recruitment during an inflammatory response. John Wiley and Sons Inc. 2023-01-09 2023-02 /pmc/articles/PMC10107448/ /pubmed/36624683 http://dx.doi.org/10.1096/fj.202201456R Text en © 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. 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 Cox, Shannon L. O'Siorain, James R. He, Yan Lordan, Ronan Naik, Amruta Tang, Soon Yew Sengupta, Shaon FitzGerald, Garret A. Carroll, Richard G. Curtis, Annie M. Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment |
title | Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment |
title_full | Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment |
title_fullStr | Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment |
title_full_unstemmed | Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment |
title_short | Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment |
title_sort | circadian disruption in lung fibroblasts enhances nf‐κb activity to exacerbate neutrophil recruitment |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107448/ https://www.ncbi.nlm.nih.gov/pubmed/36624683 http://dx.doi.org/10.1096/fj.202201456R |
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