Imperial College London
Alternate

ProfessorStuartCook

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 1346stuart.cook

 
 
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Location

 

RF 16Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Widjaja:2022:10.3390/ijms23168900,
author = {Widjaja, AA and Chothani, S and Viswanathan, S and Goh, JWT and Lim, W-W and Cook, SA},
doi = {10.3390/ijms23168900},
journal = {International Journal of Molecular Sciences},
title = {IL11 stimulates IL33 expression and proinflammatory fibroblast activation across tissues},
url = {http://dx.doi.org/10.3390/ijms23168900},
volume = {23},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Interleukin 11 (IL11) is upregulated in inflammatory conditions, where it is mostly believed to have anti-inflammatory activity. However, recent studies suggest instead that IL11 promotes inflammation by activating fibroblasts. Here, we assessed whether IL11 is pro- or anti-inflammatory in fibroblasts. Primary cultures of human kidney, lung or skin fibroblasts were stimulated with IL11 that resulted in the transient phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the sustained activation of extracellular signal-regulated protein kinases (ERK). RNA sequencing over a time course of IL11 stimulation revealed a robust but short-lived transcriptional response that was enriched for gene set hallmarks of inflammation and characterized by the upregulation of SERPINB2, TNFRSF18, Interleukin 33 (IL33), CCL20, IL1RL1, CXCL3/5/8, ICAM1 and IL11 itself. IL33 was the most upregulated signaling factor (38-fold, p = 9.8 × 10-5), and IL1RL1, its cognate receptor, was similarly increased (18-fold, p = 1.1 × 10-34). In proteomic studies, IL11 triggered a proinflammatory secretome with the notable upregulation of IL8, IL6, MCP1, CCL20 and CXCL1/5/6, which are important chemotaxins for neutrophils, monocytes, and lymphocytes. IL11 induced IL33 expression across fibroblast types, and the inhibition of STAT3 but not of MEK/ERK prevented this. These data establish IL11 as pro-inflammatory with specific importance for priming the IL33 alarmin response in inflammatory fibroblasts across tissues.
AU  - Widjaja,AA
AU  - Chothani,S
AU  - Viswanathan,S
AU  - Goh,JWT
AU  - Lim,W-W
AU  - Cook,SA
DO  - 10.3390/ijms23168900
PY  - 2022///
SN  - 1422-0067
TI  - IL11 stimulates IL33 expression and proinflammatory fibroblast activation across tissues
T2  - International Journal of Molecular Sciences
UR  - http://dx.doi.org/10.3390/ijms23168900
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36012165
UR  - http://hdl.handle.net/10044/1/99523
VL  - 23
ER  -
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