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Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by modulating function of signal transducer and activator of transcription factors
Author(s) -
CastroGarcía Flor P.,
CorralJara Karla F.,
EscobedoMelendez Griselda,
SandovalHernandez Monserrat A.,
Rosenstein Yvonne,
Roman Sonia,
Panduro Arturo,
Fierro Nora A.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12336
Subject(s) - stat protein , bilirubin , cytokine , stat , immunology , hepatitis c virus , transcription factor , biology , immune system , stat6 , tumor necrosis factor alpha , phosphorylation , virus , stat3 , endocrinology , interleukin 4 , gene , biochemistry
Summary Hepatitis A virus ( HAV ) infection is the major cause of acute liver failure in paediatric patients. The clinical spectrum of infection is variable, and liver injury is determined by altered hepatic enzyme function and bilirubin concentration. We recently reported differences in cytokine profiles between distinct HAV ‐induced clinical courses, and bilirubin has been recognized as a potential immune‐modulator. However, how bilirubin may affect cytokine profiles underlying the variability in the course of infection has not been determined. Herein, we used a transcription factor ( TF ) binding site identification approach to retrospectively analyse cytokine expression in HAV ‐infected children and to predict the entire set of TF s associated with the expression of specific cytokine profiles. The results suggested that modulation of the activity of signal transducers and activators of transcription proteins ( STAT s) may play a central role during HAV infection. This led us to compare the degree of STAT phosphorylation in peripheral blood lymphoid cells ( PBLC s) from paediatric patients with distinct levels of conjugated bilirubin ( CB ). Low CB levels in sera were associated with increased STAT ‐1 and STAT ‐5 phosphorylation. A positive correlation was observed between the serum interleukin‐6 ( IL ‐6) content and CB values, whereas higher levels of CB correlated with reduced serum IL ‐8 values and with a reduction in the proportion of PBLC s positive for STAT ‐5 phosphorylation. When CB was used to stimulate patients' PBLC s in vitro , the levels of IL ‐6 and tumour necrosis factor‐ α were increased. The data showed that bilirubin plays a role in STAT function and affects cytokine profile expression during HAV infection.