Royal College of Surgeons in Ireland
Circadian disruption in lung fibroblasts enhances....pdf (7.74 MB)

Circadian disruption in lung fibroblasts enhances NF-κB activity to exacerbate neutrophil recruitment

Download (7.74 MB)
journal contribution
posted on 2023-02-14, 17:59 authored by Shannon CoxShannon Cox, James O'SiorainJames O'Siorain, Yan HeYan He, Ronan Lordan, Amruta Naik, Soon Yew Tang, Shaon Sengupta, Garret A FitzGerald, Richard G Carroll, Annie CurtisAnnie Curtis

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. 


Irish Research Council (IRCLA/2017/110)

Science Foundation Ireland (17/CDA/4688)

Boehringer Ingelheim Fonds

Royal College of Surgeons in Ireland (RCSI)


HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI). Grant Numbers: R01HL155934-01A1, R01HL147472



The original article is available at

Published Citation

Cox SL. Et al. Circadian disruption in lung fibroblasts enhances NF-κB activity to exacerbate neutrophil recruitment. FASEB J. 2023;37(2):e22753.

Publication Date

9 January 2023

PubMed ID



  • School of Pharmacy and Biomolecular Sciences
  • Tissue Engineering Research Group (TERG)


John Wiley & Sons


  • Published Version (Version of Record)