Godbole, N;
Nyholm, I;
Hukkinen, M;
Davidson, JR;
Tyraskis, A;
Eloranta, K;
Andersson, N;
... Pakarinen, MP; + view all
(2021)
Prognostic and Pathophysiologic Significance of IL-8 (CXCL8) in Biliary Atresia.
Journal of Clinical Medicine
, 10
(12)
, Article 2705. 10.3390/jcm10122705.
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Abstract
Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 was markedly overexpressed in liver and serum of BA patients at PE (n = 88) and in serum samples obtained during postoperative follow-up (n = 40). IL-8 expression in the liver was predominantly in cholangiocytes within areas of ductular reaction. Liver IL-8 mRNA expression correlated positively with its serum concentration, bile ductular proliferation, Metavir fibrosis stage, and transcriptional markers of activated myofibroblasts (ACTA2) and cholangiocytes (KRT19). Taken together, IL-8 may mediate liver injury in BA by promoting ductular reaction and associated liver fibrogenesis. Prognostic value of serum IL-8 to predict native liver survival was limited and confined to the postoperative period after PE.
| Type: | Article |
|---|---|
| Title: | Prognostic and Pathophysiologic Significance of IL-8 (CXCL8) in Biliary Atresia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/jcm10122705 |
| Publisher version: | https://doi.org/10.3390/jcm10122705 |
| Language: | English |
| Additional information: | This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
| Keywords: | biomarker; cholangiocyte; ductular reaction; liver fibrosis; pediatric liver disease |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10134968 |
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