eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
Current issue Archive Manuscripts accepted About the journal Special Issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors Publication charge Ethical standards and procedures
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
Search
Share:
Send email
Share:
abstract:
Original paper

Interleukin 17A promotes glycolysis to activate human hepatic stellate cells by mediating the TRAF2/TRAF5/HuR/PFKFB3 axis

Tao Jiang
1
,
Shuangjie Li
1
,
Lian Tang
1
,
Yanfang Tan
1
,
Wenxian Ouyang
1

  1. Department of Hepatopathy and Endocrinology, Hunan Children’s Hospital, Changsha, Hunan Province, P.R. China
Cent Eur J Immunol 2024; 49
DOI: https://doi.org/10.5114/ceji.2024.145013
Online publish date: 2024/11/08
View full text Get citation
 
PlumX metrics:
Introduction:
Biliary atresia (BA) is an obliterating fibrous inflammatory bile duct disease in infants. Interleukin 17A (IL-17A) is abnormally expressed in patients with BA; however, the mechanism of its expression is unclear.

Material and methods:
Liver tissues from patients with BA and those with anicteric choledochal cysts (non-BA) were collected. The expression of genes and proteins was determined using RT-qPCR and western blot. Cell biological activities, including viability and proliferation, were evaluated by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assay. Glucose uptake and lactate and ATP levels were examined using commercial kits. The extracellular acidification rate (ECAR) level was evaluated by the XF96 Extracellular Flux analyzer. The interactions among TRAF2, TRAF5, and human antigen R (HuR) were validated using co-immunoprecipitation (Co-IP), RNA immunoprecipitation (RIP), and RNA pull-down.

Results:
In BA patients, IL-17A, TRAF2, TRAF5, and PFKFB3 were highly expressed, and IL-17A expression was positively correlated with PFKFB3, TRAF2, and TRAF5 expression, respectively. IL-17A elevated PFKFB3 expression and promoted glycolysis and the proliferation and fibrosis of hepatic stellate cells (HSCs), which were abolished by 2-deoxy-D-glucose (2-DG) and PFKFB3/TRAF2/TRAF5 silencing. Mechanistically, IL-17A promoted the interactions among HuR, TRAF2 and TRAF5 to form the TRAF2/TRAF5/HuR complex, thereby enhancing PFKFB3 expression.

Conclusions:
IL-17A facilitates glycolysis and HSC fibrosis by promoting TRAF2/TRAF5/HuR complex formation to regulate PFKFB3 expression.

keywords:

IL-17A, TRAF2/TRAF5/HuR complex, PFKFB3, glycolysis, biliary atresia
Termedia
About us Contact
Copyright notice Privacy policy Advertising policy Contact us
Quick links
Journals Books eBooks Events
© 2024 Termedia Sp. z o.o.
Developed by Bentus.