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p38 mitogen-activated protein kinase impairment of innate immune cells is a characteristic feature of HBeAg-negative chronic hepatitis B
dc.creator | Bakarozi M., Mavropoulos A., Bogdanos D.P., Dalekos G.N., Rigopoulou E.I. | en |
dc.date.accessioned | 2023-01-31T07:35:18Z | |
dc.date.available | 2023-01-31T07:35:18Z | |
dc.date.issued | 2020 | |
dc.identifier | 10.1111/jvh.13209 | |
dc.identifier.issn | 13520504 | |
dc.identifier.uri | http://hdl.handle.net/11615/71059 | |
dc.description.abstract | The mitogen-activated protein kinase p38 (MAPK) is implicated in the induction of immune responses by regulating the differentiation of T lymphocytes and production of cytokines. Our aim was to investigate p38MAPK phosphorylation in different stages of the natural history of hepatitis B virus (HBV) infection. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density-based centrifugation from 10 patients with HBeAg-negative chronic hepatitis B [HBeAg(−) CHB;HBV-DNA>2000IU/mL], eight patients with HBeAg-negative chronic HBV infection [HBeAg(−) CI;undetectable HBV-DNA] and 8 healthy controls (HCs). p38MAPK phosphorylation was assessed by phospho-specific flow cytometry in PBMCs and cell subsets (CD3+,CD3−,CD56+,CD56−) after stimulation with cytokines (IL-12+IL-2 and IL-12+IL-18) or nonspecific stimuli [arsenite, phorbol 12-myristate 13-acetate (PMA) and ionomycin] at 0,30,60,120 and 240 minutes using p38 phospho-specific conjugated antibodies. ΙFN-γ was determined by ELISA in PBMCs culture supernatants after stimulation with rhIL-2, rhIL-12 and rhIL-18, with and without pre-treatment with the p38 MAPK inhibitor, SB203580. HBeAg(−) CI patients showed the highest expression of phosphor-p38 MAPK in total PBMCs and subpopulations compared to HBeAg(−) CHB and HCs. A striking impairment in p38 phosphorylation was noted in CD56+ cells and in especially in NK cells (CD3-CD56+). SB203580-induced inhibition of p38MAPK phosphorylation was associated with suppression of IFN-γ production in all groups. The universal lack of p38 MAPK activation in CD56+ and in particular in NK cells from HBeAg(−) CHB patients during viremia suggests a potential cell-dependent implication of this pathway in the natural history of HBV infection. © 2019 John Wiley & Sons Ltd | en |
dc.language.iso | en | en |
dc.source | Journal of Viral Hepatitis | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073980315&doi=10.1111%2fjvh.13209&partnerID=40&md5=2007b1d1aea79b8024b0b15615087a5a | |
dc.subject | 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole | en |
dc.subject | arsenic trioxide | en |
dc.subject | CD3 antigen | en |
dc.subject | CD56 antigen | en |
dc.subject | gamma interferon | en |
dc.subject | hepatitis B(e) antigen | en |
dc.subject | interleukin 12 | en |
dc.subject | interleukin 18 | en |
dc.subject | interleukin 2 | en |
dc.subject | ionomycin | en |
dc.subject | mitogen activated protein kinase p38 | en |
dc.subject | phorbol 13 acetate 12 myristate | en |
dc.subject | virus DNA | en |
dc.subject | cytokine | en |
dc.subject | hepatitis B(e) antigen | en |
dc.subject | mitogen activated protein kinase p38 | en |
dc.subject | adult | en |
dc.subject | Article | en |
dc.subject | cell stimulation | en |
dc.subject | chronic hepatitis B | en |
dc.subject | clinical article | en |
dc.subject | controlled study | en |
dc.subject | cytokine production | en |
dc.subject | enzyme linked immunosorbent assay | en |
dc.subject | enzyme phosphorylation | en |
dc.subject | female | en |
dc.subject | flow cytometry | en |
dc.subject | human | en |
dc.subject | immunocompetent cell | en |
dc.subject | immunoregulation | en |
dc.subject | innate immunity | en |
dc.subject | male | en |
dc.subject | natural killer cell | en |
dc.subject | peripheral blood mononuclear cell | en |
dc.subject | priority journal | en |
dc.subject | protein expression | en |
dc.subject | supernatant | en |
dc.subject | virus load | en |
dc.subject | aged | en |
dc.subject | blood | en |
dc.subject | cell culture | en |
dc.subject | chronic hepatitis B | en |
dc.subject | drug effect | en |
dc.subject | immunology | en |
dc.subject | middle aged | en |
dc.subject | mononuclear cell | en |
dc.subject | pathology | en |
dc.subject | phosphorylation | en |
dc.subject | Adult | en |
dc.subject | Aged | en |
dc.subject | Cells, Cultured | en |
dc.subject | Cytokines | en |
dc.subject | Female | en |
dc.subject | Hepatitis B e Antigens | en |
dc.subject | Hepatitis B, Chronic | en |
dc.subject | Humans | en |
dc.subject | Immunity, Innate | en |
dc.subject | Leukocytes, Mononuclear | en |
dc.subject | Male | en |
dc.subject | Middle Aged | en |
dc.subject | p38 Mitogen-Activated Protein Kinases | en |
dc.subject | Phosphorylation | en |
dc.subject | Blackwell Publishing Ltd | en |
dc.title | p38 mitogen-activated protein kinase impairment of innate immune cells is a characteristic feature of HBeAg-negative chronic hepatitis B | en |
dc.type | journalArticle | en |
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