title: Protein kinase Cε regulates proliferation and cell sensitivity to TGF-1β of CD4+ T lymphocytes: implications for Hashimoto thyroiditis.
abstract: We have studied the functional role of protein kinase Cε (PKCε) in the control of human CD4(+) T cell proliferation and in their response to TGF-1β. We demonstrate that PKCε sustains CD4(+) T cell proliferation triggered in vitro by CD3 stimulation. Transient knockdown of PKCε expression decreases IL-2R chain transcription, and consequently cell surface expression levels of CD25. PKCε silencing in CD4 T cells potentiates the inhibitory effects of TGF-1β, whereas in contrast, the forced expression of PKCε virtually abrogates the inhibitory effects of TGF-1β. Being that PKCε is therefore implicated in the response of CD4 T cells to both CD3-mediated proliferative stimuli and TGF-1β antiproliferative signals, we studied it in Hashimoto thyroiditis (HT), a pathology characterized by abnormal lymphocyte proliferation and activation. When we analyzed CD4 T cells from HT patients, we found a significant increase of PKCε expression, accounting for their enhanced survival, proliferation, and decreased sensitivity to TGF-1β. The increased expression of PKCε in CD4(+) T cells of HT patients, which is described for the first time, to our knowledge, in this article, viewed in the perspective of the physiological role of PKCε in normal Th lymphocytes, adds knowledge to the molecular pathophysiology of HT and creates potentially new pharmacological targets for the therapy of this disease.
authors.affiliation: Department of Anatomy, Pharmacology and Forensic Medicine, University of Parma, 43126 Parma, Italy,
authors.forename: Prisco
authors.initials: P
authors.lastname: Mirandola
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gobbi
authors.forename: Elena
authors.initials: E
authors.lastname: Masselli
authors.forename: Cristina
authors.initials: C
authors.lastname: Micheloni
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Marcantonio
authors.forename: Valeria
authors.initials: V
authors.lastname: Queirolo
authors.forename: Paolo
authors.initials: P
authors.lastname: Chiodera
authors.forename: Tiziana
authors.initials: T
authors.lastname: Meschi
authors.forename: Marco
authors.initials: M
authors.lastname: Vitale
mesh_terms: D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D050031:Hashimoto Disease / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D051744:Protein Kinase C-epsilon / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1; C497256:Prkce protein, mouse; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon