PMID: 16525716Mar 10, 2006Paper

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

International Journal of Molecular Medicine
Tomohiro FujitaTomoyuki Masuda

Abstract

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...Continue Reading

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