Undetectable phospho-STAT1 in peripheral blood mononuclear cells from patients with chronic hepatitis C who do not respond to interferon-α therapy
Version of Record online: 28 JUN 2005
Volume 25, Issue 5, pages 987–993, October 2005
How to Cite
Aceti, A., Zechini, B., Griggi, T., Marangi, M., Pasquazzi, C., Quaranta, G. and Sorice, M. (2005), Undetectable phospho-STAT1 in peripheral blood mononuclear cells from patients with chronic hepatitis C who do not respond to interferon-α therapy. Liver International, 25: 987–993. doi: 10.1111/j.1478-3231.2005.01124.x
- Issue online: 14 JUL 2005
- Version of Record online: 28 JUN 2005
- Received 27 September 2004, accepted 25 January 2005
- chronic hepatitis C;
- interferon resistance;
Abstract: Background: Recent studies have suggested that phosphorylated signal transducers and activators of transcription 1 (STAT1) plays an important role in interferon (IFN)-mediated biological functions, including antiviral activity. Moreover, it has been demonstrated that suppressors of the cytokine signal 1 (SOCS1) negatively regulates IFN activities.
Aims: To investigate the involvement of phospho-STAT1 in the response to IFN-α therapy in patients with chronic hepatitis C and to evaluate the negative regulatory effect of SOCS1 on STAT1 activation.
Methods: Sixty-five patients with chronic hepatitis C and 25 healthy subjects were enrolled. Twenty-five of the patients had never been treated with IFN-α therapy (naive), while the remaining 40 patients had. The IFN-treated patients were divided into sustained responders (SRs) or non-responders (NRs) on the basis of their response to the antiviral therapy. Peripheral blood mononuclear cells (PBMCs) were obtained from each patient and control, and were either stimulated with IFN-α or left unstimulated. Total STAT1, phospho-STAT1 and SOCS1 were revealed by means of Western blot.
Results: Total STAT1 was equally expressed in unstimulated and stimulated PBMCs from all patients and controls. One hundred percent of the stimulated PBMCs from healthy controls and SRs, 96% from naive subjects, and 30% from NRs showed detectable phospho-STAT1. By contrast, 70% of the stimulated PBMCs from NRs showed undetectable phospho-STAT1.
Conclusions: We have demonstrated that phospho-STAT1 proteins in 70% of patients with chronic hepatitis C who do not respond to IFN treatment are undetectable, which suggests that this protein may be involved in the mediation of IFN sensitivity. The down-regulation of the Jak-STAT pathway because of SOCS1 expression may be one of the possible underlying mechanisms involved in resistance to IFN.