RGD Reference Report - Interferon-gamma down-regulates expression of tumor necrosis factor-alpha converting enzyme/a disintegrin and metalloproteinase 17 in activated hepatic stellate cells of rats. - Rat Genome Database

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Interferon-gamma down-regulates expression of tumor necrosis factor-alpha converting enzyme/a disintegrin and metalloproteinase 17 in activated hepatic stellate cells of rats.

Authors: Fujita, Tomohiro  Maesawa, Chihaya  Oikawa, Kanta  Nitta, Hiroyuki  Wakabayashi, Go  Masuda, Tomoyuki 
Citation: Fujita T, etal., Int J Mol Med. 2006 Apr;17(4):605-16.
RGD ID: 14985246
Pubmed: PMID:16525716   (View Abstract at PubMed)

Interferon-gamma (IFN-gamma) is a potent cytokine that exerts antiproliferative and antifibrogenic effects on hepatic stellate cells (HSCs). Although therapeutic application of IFN-gamma for chronic liver diseases is anticipated, the responses of activated HSCs to IFN-gamma have not been fully elucidated. To seek unknown molecules and pathways that might be responsive to IFN-gamma treatment in activated HSCs, we examined global protein expression profiles using two-dimensional gel electrophoresis combined with peptide mass fingerprint. We identified 76 increased and 59 decreased spots (>3-fold increase or decrease, total 135 spots). Database analysis suggested that the following four pathways were involved in alteration of HSCs toward a quiescent phenotype in response to IFN-gamma: i) down-regulation of the TGF-beta and PDGF signaling pathways; ii) reorganization of intermediate filaments; iii) up-regulation of fatty acid metabolism; iv) decreased expression of TNF-alpha converting enzyme (TACE)/a disintegrin and metalloproteinase 17 (ADAM17), which is responsible for shedding of the proinflammatory cytokine TNF-alpha. We confirmed down-regulation of both ADAM17 expression and soluble TNF-alpha secretion by Western blotting and real-time PCR. TNF-alpha mRNA/protein expression was not altered by IFN-gamma treatment. Our data suggest that IFN-gamma stimulation suppresses the activated phenotype of HSCs in vitro through multiple pathways. Of these pathways, down-regulation of ADAM17 expression may play a role in blocking the auto-activation mechanism of cultured HSCs through activation of the TNF-alpha signaling and shedding pathways.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
TnfRatcellular response to type II interferon  IEP  RGD 

Cellular Component

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
TnfRatextracellular space  IDA  RGD 


Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)