RGD Reference Report - Serum levels and in situ expression of TNF-alpha and TNF-alpha binding proteins in inflammatory liver diseases. - Rat Genome Database

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Serum levels and in situ expression of TNF-alpha and TNF-alpha binding proteins in inflammatory liver diseases.

Authors: Spengler, U  Zachoval, R  Gallati, H  Jung, M C  Hoffmann, R  Riethmüller, G  Pape, G 
Citation: Spengler U, etal., Cytokine. 1996 Nov;8(11):864-72. doi: 10.1006/cyto.1996.0115.
RGD ID: 14995307
Pubmed: PMID:9047083   (View Abstract at PubMed)
DOI: DOI:10.1006/cyto.1996.0115   (Journal Full-text)

Cells respond to tumour necrosis factor-alpha (TNF-alpha) via binding to 75-kDa (type A) and 55-kDa (type B) receptors which have different intracellular signalling pathways and can also circulate as soluble molecules. Both receptors are co-expressed in many tissues, but their relative contributions to cellular TNF responses is for most situations unknown. In patients with viral and non-viral inflammatory liver diseases serum TNF-alpha was determined by an immunoenzymetric assay and soluble type A and B TNF receptors (TNF-alpha r) by enzyme-linked immunological and biological assays (ELIBA). In addition, cellular expression of TNF and its binding proteins were studied in liver biopsies by an indirect immunoperoxidase technique. Secretion of TNF-alpha and upregulation of TNF-alpha r-A were particularly prominent in viral hepatitis. Strong TNF-alpha in-situ production by mononuclear cells could be demonstrated in liver biopsies from patients with acute viral hepatitis. However, TNF-alpha r-A was detected only on hepatocytes. Serum TNF-alpha r-A was elevated two-fold in relative abundance over TNF-alpha r-B and was correlated to serum TNF-alpha (r = 0.6464, P < 0.0001). Soluble TNF-alpha r levels normalized, when the viral hepatitis was cleared, and successful therapy of hepatitis B was associated with a temporary rise of TNF-alpha r-A during the initial flare of aminotransferase. Patients with alcoholic hepatitis had also evidence of TNF-alpha activation but clearly differed from patients with viral induced liver diseases: Soluble TNF-alpha r-A and TNF-alpha r-B were highly elevated in equal proportions. In situ analysis in liver biopsies revealed a distinctive pattern of TNF-alpha r expression with strong cytoplasmic staining for both TNF-alpha r-A and B on scattered hepatocytes in addition to infiltrating mononuclear cells. The data propose that TNF release during antiviral immune responses is predominantly associated with TNF-alpha r-A upregulation and shedding, whereas upregulation and shedding of TNF-alpha r-B is more prominent in alcoholic hepatitis. As cytotoxicity and apoptosis by TNF are mediated mainly via TNF-alpha r-B, our results are consistent with more severe TNF-alpha induced liver damage in alcoholic hepatitis as compared to viral hepatitis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
autoimmune hepatitis  IEP 14995307protein:increased expression:serum (human)RGD 
autoimmune hepatitis  ISOTNF (Homo sapiens)14995307; 14995307protein:increased expression:serum (human)RGD 
Chronic Hepatitis C  IEP 14995307protein:increased expression:serum (human)RGD 
Chronic Hepatitis C  ISOTNF (Homo sapiens)14995307; 14995307protein:increased expression:serum (human)RGD 
hepatitis A  IEP 14995307protein:increased expression:serum (human)RGD 
hepatitis A  ISOTNF (Homo sapiens)14995307; 14995307protein:increased expression:serum (human)RGD 
primary biliary cholangitis  IEP 14995307protein:increased expression:serum (human)RGD 
primary biliary cholangitis  ISOTNF (Homo sapiens)14995307; 14995307protein:increased expression:serum (human)RGD 
primary sclerosing cholangitis  IEP 14995307protein:increased expression:serum (human)RGD 
primary sclerosing cholangitis  ISOTNF (Homo sapiens)14995307; 14995307protein:increased expression:serum (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)


Additional Information