RGD Reference Report - Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. - Rat Genome Database

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Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis.

Authors: Zimmermann, Henning W  Seidler, Sebastian  Gassler, Nikolaus  Nattermann, Jacob  Luedde, Tom  Trautwein, Christian  Tacke, Frank 
Citation: Zimmermann HW, etal., PLoS One. 2011;6(6):e21381. doi: 10.1371/journal.pone.0021381. Epub 2011 Jun 22.
RGD ID: 26884357
Pubmed: PMID:21731723   (View Abstract at PubMed)
PMCID: PMC3120868   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0021381   (Journal Full-text)


BACKGROUND: Interleukin-8 (IL-8, CXCL8) is a potent chemoattractant for neutrophils and contributes to acute liver inflammation. Much less is known about IL-8 in chronic liver diseases (CLD), but elevated levels were reported from alcoholic and hepatitis C-related CLD. We investigated the regulation of IL-8, its receptors CXCR1 and CXCR2 and possible IL-8 responding cells in CLD patients.
METHODOLOGY: Serum IL-8 levels were measured in CLD patients (n = 200) and healthy controls (n = 141). Intrahepatic IL-8, CXCR1 and CXCR2 gene expression was quantified from liver samples (n = 41), alongside immunohistochemical neutrophil (MPO) and macrophage (CD68) stainings. CXCR1 and CXCR2 expression was analyzed on purified monocytes from patients (n = 111) and controls (n = 31). In vitro analyses explored IL-8 secretion by different leukocyte subsets.
PRINCIPAL FINDINGS: IL-8 serum levels were significantly increased in CLD patients, especially in end-stage cirrhosis. Interestingly, patients with cholestatic diseases exhibited highest IL-8 serum concentrations. IL-8 correlated with liver function, inflammatory cytokines and non-invasive fibrosis markers. Intrahepatically, IL-8 and CXCR1 expression were strongly up-regulated. However, intrahepatic IL-8 could only be associated to neutrophil infiltration in patients with primary biliary cirrhosis (PBC). In non-cholestatic cirrhosis, increased IL-8 and CXCR1 levels were associated with hepatic macrophage accumulation. In line, CXCR1, but not CXCR2 or CXCR3, expression was increased on circulating monocytes from cirrhotic patients. Moreover, monocyte-derived macrophages from CLD patients, especially the non-classical CD16⁺ subtype, displayed enhanced IL-8 secretion in vitro.
CONCLUSIONS: IL-8 is strongly activated in CLD, thus likely contributing to hepatic inflammation. Our study suggests a novel role of IL-8 for recruitment and activation of hepatic macrophages via CXCR1 in human liver cirrhosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCL8Humanliver cirrhosis disease_progressionIEP mRNA more ...RGD 
Cxcl15Mouseliver cirrhosis disease_progressionISOCXCL8 (Homo sapiens)mRNA more ...RGD 
CXCL8Humanprimary biliary cholangitis  IEP mRNA:increased expression:liver (human)RGD 
Cxcl15Mouseprimary biliary cholangitis  ISOCXCL8 (Homo sapiens)mRNA:increased expression:liver (human)RGD 

Objects Annotated

Genes (Mus musculus)
Cxcl15  (C-X-C motif chemokine ligand 15)

Genes (Homo sapiens)
CXCL8  (C-X-C motif chemokine ligand 8)


Additional Information