Rottlerin inhibits human T cell responses

[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.

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Springael, Cécile

Thomas, Séverine

Rahmouni, Souad ; 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

Language :

English

Title :

Rottlerin inhibits human T cell responses

Publication date :

15 February 2007

Journal title :

Biochemical Pharmacology

ISSN :

0006-2952

eISSN :

1873-2968

Publisher :

Pergamon-Elsevier Science Ltd, Oxford, United Kingdom

Volume :

Issue :

Pages :

515-525

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 26 January 2009

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