guest ::
| Home > Publications database > PP1α and Cofilin regulate nuclear translocation of NFkB and promote expression of the anti-inflammatory cytokine IL-10 by T-cells. |
| Home > Publications database > PP1α and Cofilin regulate nuclear translocation of NFkB and promote expression of the anti-inflammatory cytokine IL-10 by T-cells. |
| Journal Article | DKFZ-2018-01464 |
; ; ; ; ;
2018
Soc.
Washington, DC
This record in other databases: 
Please use a persistent id in citations: doi:10.1128/MCB.00041-18
Abstract: 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.
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
|
The record appears in these collections: |
