The role of STAT proteins in the regulation of the response to the interferone α therapy in chronic hepatitis C
Authors:
J. Ehrmann jr. 1; K. Aiglová 2; J. Ehrmann 2; J. Palas 3; P. Kümpel 4
Authors‘ workplace:
Laboratoř molekulární patologie Ústavu patologie Lékařské fakulty UP, Olomouc, přednosta doc. MUDr. M. Tichý, CSc.
1; II. interní klinika Lékařské fakulty UP a FN, Olomouc, přednosta prof. MUDr. J. Ehrmann, CSc.
2; Oddělení patologie Slezské nemocnice, Opava, přednosta prim. MUDr. J. Palas
3; Infekční oddělení Slezské nemocnice, Opava, přednosta prim. MUDr. P. Kümpel
4
Published in:
Vnitř Lék 2006; 52(2): 167-172
Category:
Review
Overview
The currently used standard treatment for chronic hepatitis C using a dual combination of IFNα/RBV is only successful in 50 % cases. With the exception of some clinical and biochemical factors, degree of inflammation (grading) and degree of fibrosis (staging), there are no other known markers which may serve as valid predictors of response to therapy. Interference of hepatitis C virus (HCV) with signaling pathways modulated by JAK-STAT, ERK 1/2, NFκB and MAP proteins is one mechanism which may influence the interaction between HCV and IFNα. These proteins regulate different cell processes such as activation of cytokines, activation of apoptosis, regulation of cell proliferation etc. Therefore, it is possible that impaired signaling or inhibition/dysregulation of some of these proteins by HCV infection may cause resistance to IFNα treatment. This review is completed by results of preliminary study the aim of which was immunohistochemical assessment and analysis of expression of STAT 2, 3 proteins, their inhibitors SOCS 2, 3 and PIAS 3 and proteins JAK 1 and ERK 1/2 in liver biopsies of 26 patients with chronic hepatitis C treated by dual combination IFNα/RBV and subsequent correlation of the results of immunohistochemical analysis (histoscore) with histological picture and clinical response to treatment. The results shows increased expression of STAT 3, STAT 2 and ERK 1 proteins and decreased expression of SOCS 3 and SOCS 2 in hepatocytes of patients with more marked inflammation and fibrosis. In patients with sustained virological response there was increased expression of SOCS 3 and JAK 1 and decreased expression of SOCS 2. Relapse was associated with increased expression of SOCS 3 and PIAS 3. However, owing to the small sample size, the results only approximated statistical significance, but we suggest that proteins of STAT family and their inhibitors SOCS and PIAS probably play an important regulatory role during response to treatment for chronic hepatitis C.
Key words:
hepatitis C - interferon α - liver biopsy - immunohistochemistry - STAT - SOCS - prediction
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