Home > Publications database > PP1α and Cofilin regulate nuclear translocation of NFkB and promote expression of the anti-inflammatory cytokine IL-10 by T-cells. > print |
001 | 137584 | ||
005 | 20240229105111.0 | ||
024 | 7 | _ | |a 10.1128/MCB.00041-18 |2 doi |
024 | 7 | _ | |a pmid:30181394 |2 pmid |
024 | 7 | _ | |a 0270-7306 |2 ISSN |
024 | 7 | _ | |a 1098-5549 |2 ISSN |
024 | 7 | _ | |a altmetric:48247182 |2 altmetric |
037 | _ | _ | |a DKFZ-2018-01464 |
041 | _ | _ | |a eng |
082 | _ | _ | |a 570 |
100 | 1 | _ | |a Wabnitz, Guido H |b 0 |
245 | _ | _ | |a PP1α and Cofilin regulate nuclear translocation of NFkB and promote expression of the anti-inflammatory cytokine IL-10 by T-cells. |
260 | _ | _ | |a Washington, DC |c 2018 |b Soc. |
336 | 7 | _ | |a article |2 DRIVER |
336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1540988944_20835 |2 PUB:(DE-HGF) |
336 | 7 | _ | |a ARTICLE |2 BibTeX |
336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
520 | _ | _ | |a While several protein serine-threonine kinases control cytokine production by T-cells, the roles of serine-threonine phosphatases are largely unexplored. Here, we analysed the involvement of protein phosphatase-1α (PP1α) in cytokine synthesis following costimulation of primary human T-cells. SiRNA-mediated knock-down of PP1α (PP1KD) or expression of a dominant-negative PP1α (D95N-PP1) drastically diminished IL-10 production. Focusing on a key transcriptional activator of human IL-10, we demonstrate that nuclear translocation of NF-kB was significantly inhibited in PP1KD or D95N-PP1 cells. Interestingly, knockdown of cofilin, a known substrate of PP1 containing a nuclear localization signal, also prevented nuclear accumulation of NF-kB. Expression of a constitutively active non-phosphorylatable S3A-cofilin in D95N-PP1 cells restored nuclear translocation of NF-kB and IL-10 expression. Sub-population analysis revealed that defective nuclear translocation of NF-kB was most prominent in CD4+CD45RA-CXCR3- T-cells that included IL-10-producing TH2 cells. Together these findings reveal novel functions for PP1α and its substrate cofilin in T-cells namely the regulation of the nuclear translocation of NF-kB and promotion of IL-10 production. These data suggest that stimulation of PP1α could limit the overwhelming immune responses seen in chronic inflammatory diseases. |
536 | _ | _ | |a 317 - Translational cancer research (POF3-317) |0 G:(DE-HGF)POF3-317 |c POF3-317 |f POF III |x 0 |
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700 | 1 | _ | |a Kirchgessner, Henning |b 1 |
700 | 1 | _ | |a Jahraus, Beate |b 2 |
700 | 1 | _ | |a Umansky, Ludmila |0 P:(DE-He78)d5882ffec9d5dea0104c7d33165e4a45 |b 3 |u dkfz |
700 | 1 | _ | |a Shenolikar, Shirish |b 4 |
700 | 1 | _ | |a Samstag, Yvonne |b 5 |
773 | _ | _ | |a 10.1128/MCB.00041-18 |g p. MCB.00041-18mcb;MCB.00041-18v1 |0 PERI:(DE-600)1474919-1 |n 22 |p e00041-18 |t Molecular and cellular biology |v 38 |y 2018 |x 1098-5549 |
909 | C | O | |o oai:inrepo02.dkfz.de:137584 |p VDB |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 3 |6 P:(DE-He78)d5882ffec9d5dea0104c7d33165e4a45 |
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914 | 1 | _ | |y 2018 |
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