Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.
| dc.contributor.author | Wabnitz, Guido H | |
| dc.contributor.author | Kirchgessner, Henning | |
| dc.contributor.author | Jahraus, Beate | |
| dc.contributor.author | Umansky, Ludmila | |
| dc.contributor.author | Shenolikar, Shirish | |
| dc.contributor.author | Samstag, Yvonne | |
| dc.date.accessioned | 2019-03-01T23:42:22Z | |
| dc.date.available | 2019-03-01T23:42:22Z | |
| dc.date.issued | 2018-11 | |
| dc.date.updated | 2019-03-01T23:42:12Z | |
| dc.description.abstract | While several protein serine/threonine kinases control cytokine production by T cells, the roles of serine/threonine phosphatases are largely unexplored. Here, we analyzed the involvement of protein phosphatase 1α (PP1α) in cytokine synthesis following costimulation of primary human T cells. Small interfering RNA (siRNA)-mediated knockdown of PP1α (PP1KD) or expression of a dominant negative PP1α (D95N-PP1) drastically diminished interleukin-10 (IL-10) production. Focusing on a key transcriptional activator of human IL-10, we demonstrate that nuclear translocation of NF-κB 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-κB. Expression of a constitutively active nonphosphorylatable S3A-cofilin in D95N-PP1 cells restored nuclear translocation of NF-κB and IL-10 expression. Subpopulation analysis revealed that defective nuclear translocation of NF-κB 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-κB and promotion of IL-10 production. These data suggest that stimulation of PP1α could limit the overwhelming immune responses seen in chronic inflammatory diseases. | |
| dc.identifier | MCB.00041-18 | |
| dc.identifier.issn | 0270-7306 | |
| dc.identifier.issn | 1098-5549 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Informa UK Limited | |
| dc.relation.ispartof | Molecular and cellular biology | |
| dc.relation.isversionof | 10.1128/mcb.00041-18 | |
| dc.subject | T-cell activation | |
| dc.subject | cytokines | |
| dc.subject | phosphatase | |
| dc.title | Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Shenolikar, Shirish|0000-0003-0540-6328 | |
| pubs.issue | 22 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Psychiatry & Behavioral Sciences, Translational Neuroscience | |
| pubs.organisational-group | Psychiatry & Behavioral Sciences | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.publication-status | Published | |
| pubs.volume | 38 |
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