Reference : Rottlerin inhibits human T cell responses
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
Rottlerin inhibits human T cell responses
Springael, Cécile [> > > >]
Thomas, Séverine [ > > ]
Rahmouni, Souad mailto [Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation >]
Vandamme, Arnaud [Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation >]
Goldman, Michel [> > > >]
Willems, Fabienne [ > > ]
Vosters, Olivier [> > > >]
Biochemical Pharmacology
Pergamon-Elsevier Science Ltd
Yes (verified by ORBi)
[en] rottlerin ; human T cells ; TCR/CD28 stimulation ; protein kinase C theta
[en] 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/antiCD28 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. (c) 2006 Elsevier Inc. All rights reserved.
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