Title
Flow cytometric analysis of phospho-p38 mitogen-activated kinase (MAPK): p38 MAPK does not mediate the effect of adalimumab on peripheral T cell cytokine production in rheumatoid arthritisFlow cytometric analysis of phospho-p38 mitogen-activated kinase (MAPK): p38 MAPK does not mediate the effect of adalimumab on peripheral T cell cytokine production in rheumatoid arthritis
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Translational Pathophysiological Research (TPR)
Faculteit Geneeskunde
Publication type
article
Publication
Philadelphia, Pa,
Subject
Human medicine
Source (journal)
Cytokine. - Philadelphia, Pa
Volume/pages
47(2009):3, p. 178-184
ISSN
1043-4666
ISI
000269784300006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background: The therapeutic effect of TNFá inhibition in rheumatoid arthritis (RA) is accompanied by an altered peripheral T cell cytokine profile, but the underlying mechanisms are not well known. In CD4+ T cells, TNF signalling includes the p38 MAP kinase (MAPK) pathway, which is also involved in proliferation and production of IL-4 and IFNã. Methods: Phosphorylation of p38 MAPK was analysed flow cytometrically in peripheral blood mononuclear cells (PBMC) from healthy individuals and RA patients before and after adalimumab therapy. Cytokine production by CD3/CD28-stimulated PBMC was measured in the supernatant. Results: Despite a transient activation of p38 MAPK in response to cellular stress from the cell separation, a significant decrease of spontaneous p38 MAPK phosphorylation was observed after adalimumab, compared to RA patients with active disease. Brief stimulation with TNFá/IL-1â significantly activated p38 MAPK after but not before adalimumab therapy. In CD3/CD28-stimulated PBMC, significantly less p38 MAPK activation and increased IFNã production were observed after adalimumab therapy. Conclusion: In rheumatoid arthritis, adalimumab therapy decreases the phosphorylation of p38 MAPK except for its response to TNF/IL-1, while enhancing the production of IFNã. This suggests that p38 MAPK is not directly involved in the effect of TNF inhibition on cytokine production.
E-info
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