| Title: |
Prognostic and Pathophysiologic Significance of IL-8 (CXCL8) in Biliary Atresia |
| Authors: |
Godbole, Nimish; Nyholm, Iiris Aurora; Hukkinen, Maria; Davidson, Joseph R.; Tyraskis, Athanasios; Eloranta, Katja; Andersson, Noora; Lohi, Jouko; Heikkilä, Päivi; Kyrönlahti, Antti; Pihlajoki, Marjut; Davenport, Mark; Heikinheimo, Markku; Pakarinen, Mikko P. |
| Contributors: |
Children's Hospital; University of Helsinki; HUS Shared Group Services; HUS Children and Adolescents; Lastenkirurgian yksikkö; HUSLAB; University Management; Department of Pathology; Medicum; Clinicum; Helsinki One Health (HOH); Developmental and tumor biology research group |
| Publisher Information: |
MDPI |
| Publication Year: |
2021 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
General medicine; internal medicine and other clinical medicine; biomarker; cholangiocyte; ductular reaction; liver fibrosis; pediatric liver disease; NATIVE LIVER; EXPRESSION; CELLS; FIBROGENESIS; PORTOENTEROSTOMY; TRANSPLANTATION; CENTRALIZATION; INTERLEUKIN-8; INFLAMMATION; CHOLANGITIS |
| Description: |
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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISBN: |
978-0-00-666909-8; 0-00-666909-3 |
| Relation: |
https://hdl.handle.net/10138/332372; 000666909300001 |
| Availability: |
https://hdl.handle.net/10138/332372 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.A2DC24EA |
| Database: |
BASE |