Imperial College London
Alternate

ProfessorStuartCook

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
//

Contact

 

+44 (0)20 3313 1346stuart.cook

 
 
//

Location

 

RF 16Sydney StreetRoyal Brompton Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Ng:2022:10.3390/ijms23073549,
author = {Ng, B and Viswanathan, S and Widjaja, AA and Lim, W-W and Shekeran, SG and Goh, JWT and Tan, J and Kuthubudeen, F and Lim, SY and Xie, C and Schafer, S and Adami, E and Cook, SA},
doi = {10.3390/ijms23073549},
journal = {International Journal of Molecular Sciences},
pages = {1--17},
title = {IL11 activates pancreatic stellate cells and causes pancreatic inflammation, fibrosis and atrophy in a mouse model of pancreatitis},
url = {http://dx.doi.org/10.3390/ijms23073549},
volume = {23},
year = {2022}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Interleukin-11 (IL11) is important for fibrosis and inflammation, but its role in the pancreas is unclear. In pancreatitis, fibrosis, inflammation and organ dysfunction are associated with pancreatic stellate cell (PSC)-to-myofibroblast transformation. Here, we show that IL11 stimulation of PSCs, which specifically express IL11RA in the pancreas, results in transient STAT3 phosphorylation, sustained ERK activation and PSC activation. In contrast, IL6 stimulation of PSCs caused sustained STAT3 phosphorylation but did not result in ERK activation or PSC transformation. Pancreatitis factors, including TGFβ, CTGF and PDGF, induced IL11 secretion from PSCs and a neutralising IL11RA antibody prevented PSC activation by these stimuli. This revealed an important ERK-dependent role for autocrine IL11 activity in PSCs. In mice, IL11 was increased in the pancreas after pancreatic duct ligation, and in humans, IL11 and IL11RA levels were elevated in chronic pancreatitis. Following pancreatic duct ligation, administration of anti-IL11RA to mice reduced pathologic (ERK, STAT, NF-κB) signalling, pancreatic atrophy, fibrosis and pro-inflammatory cytokine (TNFα, IL6 and IL1β) levels. This is the first description of IL11-mediated activation of PSCs, and the data suggest IL11 as a stromal therapeutic target in pancreatitis.
AU  - Ng,B
AU  - Viswanathan,S
AU  - Widjaja,AA
AU  - Lim,W-W
AU  - Shekeran,SG
AU  - Goh,JWT
AU  - Tan,J
AU  - Kuthubudeen,F
AU  - Lim,SY
AU  - Xie,C
AU  - Schafer,S
AU  - Adami,E
AU  - Cook,SA
DO  - 10.3390/ijms23073549
EP  - 17
PY  - 2022///
SN  - 1422-0067
SP  - 1
TI  - IL11 activates pancreatic stellate cells and causes pancreatic inflammation, fibrosis and atrophy in a mouse model of pancreatitis
T2  - International Journal of Molecular Sciences
UR  - http://dx.doi.org/10.3390/ijms23073549
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000780761900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.mdpi.com/1422-0067/23/7/3549
UR  - http://hdl.handle.net/10044/1/105617
VL  - 23
ER  -
Download