cAMP regulates IL-10 production by normal human T lymphocytes at multiple levels: A potential role for MEF2

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dc.contributor.authorLiopeta, K.en
dc.contributor.authorBoubali, S.en
dc.contributor.authorVirgilio, L.en
dc.contributor.authorThyphronitis, G.en
dc.contributor.authorMavrothalassitis, G.en
dc.contributor.authorDimitracopoulos, G.en
dc.contributor.authorPaliogianni, F.en
dc.date.accessioned2015-11-24T16:34:14Z
dc.date.available2015-11-24T16:34:14Z
dc.identifier.issn0161-5890-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/7779
dc.rightsDefault Licence-
dc.subjectcampen
dc.subjectil-10en
dc.subjectt lymphocytesen
dc.subjectmef2en
dc.subjectpkaen
dc.subjectmyocyte-enhancer factor-2en
dc.subjectprotein-kinase-aen
dc.subjectnecrosis-factor-alphaen
dc.subjectgene-expressionen
dc.subjecttranscription factorsen
dc.subjectinterleukin-10 promoteren
dc.subjectcell-proliferationen
dc.subjectmuscle developmenten
dc.subjectprostaglandin e-2en
dc.subjectbinding proteinen
dc.titlecAMP regulates IL-10 production by normal human T lymphocytes at multiple levels: A potential role for MEF2en
heal.abstractSignal transduction by the cAMP/cAMP-dependent protein kinase A (PKA) pathway is triggered through multiple receptors and is important for many processes in a variety of cells. In T cells, the engagement of the TCR-CD3 complex induces CAMP, a second messenger that controls immune response. IL-10, produced by a variety of lymphocyte subpopulations, is an important regulator of this response exerting a wide range of immunomodulatory actions. Elevation of cAMP has been shown to increase IL-10 production by monocytes. However, the mechanism of cAMP mediated regulation of IL-10 production by T lymphocytes remains unclear. In this study using normal peripheral T lymphocytes stimulated either through the TCR-CD3 complex or the TCR-CD3 and the CD28 molecule, we show that IL-10 is produced mainly by memory T lymphocytes after either way of stimulation and is drastically inhibited (70-90%) by CAMP elevating agents. cAMP mediated inhibition was reversed by the use of the specific PKA inhibitor Rp-8-Br-cAMP but not by the addition of exogenous rhIL-2, indicating that the inhibitory effect depends on PKA activation and is not secondary to IL-2 inhibition, Inhibition is taking place at both transcriptional and posttranscriptional level. Transfection of a luciferase reporter plasmid carrying the IL-10 promoter in T cells, revealed that TCR/CD28-induced activation was inhibited by 60% by cAMP elevation. The most sensitive part to cAMP mediated inhibition was a fragment of 135 bp Upstream of TATA box, which contains multiple binding sites for MEF-2. Overexpression of MEF-2 in the same cells increased IL-10 promoter activity by 2.5-fold. Stimulation through TCR/CD28 increased MEF-2 binding in its Corresponding binding sites which was inhibited by 80% in the presence of cAMP elevating agents. These results suggest that the inhibitory effect of cAMP on IL-10 production by normal peripheral T lymphocytes is cell type and stimulus specific, exerted on multiple levels and involves MEF2 transcription factor. (C) 2008 Elsevier Ltd. All rights reserved.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primaryDOI 10.1016/j.molimm.2008.10.025-
heal.identifier.secondary<Go to ISI>://000262810400005-
heal.identifier.secondaryhttp://ac.els-cdn.com/S0161589008007438/1-s2.0-S0161589008007438-main.pdf?_tid=44e2cca8468d07c16b2bdd726b6f207a&acdnat=1336730790_1fe974404445ea4d356893933d908dab-
heal.journalNameMol Immunolen
heal.journalTypepeer reviewed-
heal.languageen-
heal.publicationDate2009-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιώνel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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