Dr Ronan Lordan

Available to discuss new collaborations, science outreach or speaking opportunities. Feel free to make contact via email or twitter.



Institute for Translational Medicine and Therapeutics

Perelman School of Medicine, University of Pennsylvania



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


Journal article


Shannon L Cox, James R. O’Siorain, Yan He, R. Lordan, A. Naik, S. Tang, Shaon Sengupta, G. FitzGerald, R. Carroll, Annie M. Curtis
The FASEB Journal, 2023

Semantic Scholar DOI PubMed
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Cite

APA   Click to copy
Cox, S. L., O’Siorain, J. R., He, Y., Lordan, R., Naik, A., Tang, S., … Curtis, A. M. (2023). Circadian disruption in lung fibroblasts enhances NF-κB activity to exacerbate neutrophil recruitment. The FASEB Journal.


Chicago/Turabian   Click to copy
Cox, Shannon L, James R. O’Siorain, Yan He, R. Lordan, A. Naik, S. Tang, Shaon Sengupta, G. FitzGerald, R. Carroll, and Annie M. Curtis. “Circadian Disruption in Lung Fibroblasts Enhances NF-ΚB Activity to Exacerbate Neutrophil Recruitment.” The FASEB Journal (2023).


MLA   Click to copy
Cox, Shannon L., et al. “Circadian Disruption in Lung Fibroblasts Enhances NF-ΚB Activity to Exacerbate Neutrophil Recruitment.” The FASEB Journal, 2023.


BibTeX   Click to copy

@article{shannon2023a,
  title = {Circadian disruption in lung fibroblasts enhances NF-κB activity to exacerbate neutrophil recruitment.},
  year = {2023},
  journal = {The FASEB Journal},
  author = {Cox, Shannon L and O’Siorain, James R. and He, Yan and Lordan, R. and Naik, A. and Tang, S. and Sengupta, Shaon and FitzGerald, G. and Carroll, R. and Curtis, Annie M.}
}

Abstract

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.


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