Rottlerin inhibits human T cell responses
Copyright policy )Rottlerin inhibits human T cell responses
Rottlerin is a pharmacological inhibitor of protein kinase C (PKC) theta, a novel PKC selectively expressed in T lymphocytes. PKC theta is known to regulate T cell receptor (TCR)/CD28 signalling pathways in T lymphocytes, but the impact of PKC theta inhibition on human T cell responses remains undefined. In this work, we describe the effects of rottlerin on the responses of CD4+ and CD8+ human T lymphocytes upon polyclonal activation. We observed a dose-dependent inhibition of CD4+ and CD8+ T cell proliferation in response to anti-CD3/anti-CD28 antibodies stimulation in the presence of rottlerin. This inhibition was associated with impaired CD25 expression and decreased interleukin (IL)-2 production in activated T cells. In contrast, rottlerin did not alter IL-2-induced T cell proliferation. Furthermore, we demonstrated that rottlerin blocked interferon (IFN) gamma, IL-10 and IL-13 mRNA expression in TCR/CD28 activated CD4+ T cells. These findings place rottlerin as a potent immunosuppressive agent for the development of novel therapies in T cell mediated immune disorders.
- University of Liège Belgium
- Université Libre de Bruxelles Belgium
Antigens, Differentiation, T-Lymphocyte, CD4-Positive T-Lymphocytes, Th1 Cells -- drug effects, CD28 -- genetics, CD8-Positive T-Lymphocytes -- metabolism, Interleukin-2 -- antagonists & inhibitors, CD8-Positive T-Lymphocytes, rottlerin, Cell Proliferation -- drug effects, CD28 -- metabolism, CD8 -- metabolism, Protein Tyrosine Phosphatases -- genetics, Enzyme Inhibitors -- pharmacology, Interleukin-2 Receptor alpha Subunit -- metabolism, TCR/CD28 stimulation, Non-Receptor, Propidium -- metabolism, Human health sciences, Enzyme Inhibitors, human T cells, Pharmacy, pharmacology & toxicology, T-Lymphocyte -- metabolism, Cytokines -- genetics, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-2 -- immunology, Intracellular Signaling Peptides and Proteins, Pharmacie, pharmacologie & toxicologie, Sciences bio-médicales et agricoles, CD4-Positive T-Lymphocytes -- drug effects, Flow Cytometry, Cytokines -- metabolism, CD4-Positive T-Lymphocytes -- metabolism, Differentiation, Cytokines, Drug, Western, CD8-Positive T-Lymphocytes -- drug effects, CD -- metabolism, CD8 Antigens, Blotting, Western, Intracellular Signaling Peptides and Proteins -- genetics, Messenger -- genetics, Acetophenones -- pharmacology, Sciences de la santé humaine, Dose-Response Relationship, Protein Tyrosine Phosphatases -- metabolism, CD28 Antigens, Antigens, CD, Benzopyrans -- pharmacology, Humans, Benzopyrans, Lectins, C-Type, Antigens, Cell Proliferation, protein kinase C theta, Dose-Response Relationship, Drug, Intracellular Signaling Peptides and Proteins -- metabolism, Interleukin-2 Receptor alpha Subunit, Acetophenones, Messenger -- metabolism, Protein Kinase C-delta -- antagonists & inhibitors, Sirolimus -- pharmacology, Interleukin-2 Receptor alpha Subunit -- genetics, Calcium -- metabolism, RNA, Interleukin-2, Calcium, CD4-Positive T-Lymphocytes -- cytology, CD8-Positive T-Lymphocytes -- cytology, Protein Tyrosine Phosphatases
Antigens, Differentiation, T-Lymphocyte, CD4-Positive T-Lymphocytes, Th1 Cells -- drug effects, CD28 -- genetics, CD8-Positive T-Lymphocytes -- metabolism, Interleukin-2 -- antagonists & inhibitors, CD8-Positive T-Lymphocytes, rottlerin, Cell Proliferation -- drug effects, CD28 -- metabolism, CD8 -- metabolism, Protein Tyrosine Phosphatases -- genetics, Enzyme Inhibitors -- pharmacology, Interleukin-2 Receptor alpha Subunit -- metabolism, TCR/CD28 stimulation, Non-Receptor, Propidium -- metabolism, Human health sciences, Enzyme Inhibitors, human T cells, Pharmacy, pharmacology & toxicology, T-Lymphocyte -- metabolism, Cytokines -- genetics, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-2 -- immunology, Intracellular Signaling Peptides and Proteins, Pharmacie, pharmacologie & toxicologie, Sciences bio-médicales et agricoles, CD4-Positive T-Lymphocytes -- drug effects, Flow Cytometry, Cytokines -- metabolism, CD4-Positive T-Lymphocytes -- metabolism, Differentiation, Cytokines, Drug, Western, CD8-Positive T-Lymphocytes -- drug effects, CD -- metabolism, CD8 Antigens, Blotting, Western, Intracellular Signaling Peptides and Proteins -- genetics, Messenger -- genetics, Acetophenones -- pharmacology, Sciences de la santé humaine, Dose-Response Relationship, Protein Tyrosine Phosphatases -- metabolism, CD28 Antigens, Antigens, CD, Benzopyrans -- pharmacology, Humans, Benzopyrans, Lectins, C-Type, Antigens, Cell Proliferation, protein kinase C theta, Dose-Response Relationship, Drug, Intracellular Signaling Peptides and Proteins -- metabolism, Interleukin-2 Receptor alpha Subunit, Acetophenones, Messenger -- metabolism, Protein Kinase C-delta -- antagonists & inhibitors, Sirolimus -- pharmacology, Interleukin-2 Receptor alpha Subunit -- genetics, Calcium -- metabolism, RNA, Interleukin-2, Calcium, CD4-Positive T-Lymphocytes -- cytology, CD8-Positive T-Lymphocytes -- cytology, Protein Tyrosine Phosphatases
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