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Prognostic and Pathophysiologic Significance of IL-8 (CXCL8) in Biliary Atresia

Title: Prognostic and Pathophysiologic Significance of IL-8 (CXCL8) in Biliary Atresia
Authors: Nimish Godbole; Iiris Nyholm; Maria Hukkinen; Joseph R. Davidson; Athanasios Tyraskis; Katja Eloranta; Noora Andersson; Jouko Lohi; Päivi Heikkilä; Antti Kyrönlahti; Marjut Pihlajoki; Mark Davenport; Markku Heikinheimo; Mikko P. Pakarinen
Source: Journal of Clinical Medicine, Vol 10, Iss 2705, p 2705 (2021)
Publisher Information: MDPI AG
Publication Year: 2021
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: biomarker; cholangiocyte; ductular reaction; liver fibrosis; pediatric liver disease; Medicine
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.
Document Type: article in journal/newspaper
Language: English
Relation: https://www.mdpi.com/2077-0383/10/12/2705; https://doaj.org/toc/2077-0383; https://doaj.org/article/59ef1fe0bf6f4405873da32c3461276c
DOI: 10.3390/jcm10122705
Availability: https://doi.org/10.3390/jcm10122705; https://doaj.org/article/59ef1fe0bf6f4405873da32c3461276c
Accession Number: edsbas.4E9862F4
Database: BASE