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Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells

A tissue antigen, HLA-B27, is strongly associated with a group of rheumatic diseases called spondyloarthritides. Despite the intensive research, the exact role of HLA-B27 in the pathogenesis of these diseases is still unclear. Here we studied whether HLA-B27 modulates the phosphorylation of signal t...

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Autores principales: Ruuska, Marja, Sahlberg, Anna S., Granfors, Kaisa, Penttinen, Markus A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549911/
https://www.ncbi.nlm.nih.gov/pubmed/23349666
http://dx.doi.org/10.1371/journal.pone.0050684
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author Ruuska, Marja
Sahlberg, Anna S.
Granfors, Kaisa
Penttinen, Markus A.
author_facet Ruuska, Marja
Sahlberg, Anna S.
Granfors, Kaisa
Penttinen, Markus A.
author_sort Ruuska, Marja
collection PubMed
description A tissue antigen, HLA-B27, is strongly associated with a group of rheumatic diseases called spondyloarthritides. Despite the intensive research, the exact role of HLA-B27 in the pathogenesis of these diseases is still unclear. Here we studied whether HLA-B27 modulates the phosphorylation of signal transducer and activator of transcription 1 (STAT-1) serine 727 residue and the localization of STAT-1 in Salmonella-infected human monocytic cells. In addition, we studied the role of signaling molecule double-stranded RNA activated protein kinase (PKR) in these modulatory effects. U937 human monocytic cell transfectants stably expressing wild type HLA-B27 or mutated HLA-B27 heavy chains with amino acid substitutions in the B pocket were prepared. The PMA-differentiated cells were infected with S. enteritidis. Western blotting was used to detect the phosphorylation of STAT-1, and to visualize the localization of STAT-1 in the cells confocal microscopy was used. Specific inhibitors were employed to study the role of PKR in STAT-1 phosphorylation. We discovered that the phosphorylation of STAT-1 serine 727 is prolonged in cells expressing misfolding forms of HLA-B27 after S. enteritidis infection, whereas in mock cells and in cells expressing mutated, non-misfolding HLA-B27 the phosphorylation of serine 727 is transient. Interestingly, STAT-1 serine 727 phosphorylation is partly dependent on PKR. In addition, more STAT-1 is localized in the nucleus of HLA-B27-expressing cells, even before an external trigger, when compared to mock cells. In conclusion, our results show that the phosphorylation of STAT-1 serine 727 residue is prolonged in HLA-B27-expressing monocyte-macrophage U937 cells after bacterial infection. This is of interest since the phosphorylation of serine 727 on STAT-1 is suggested to contribute to macrophage activation and promote inflammatory responses. Therefore, our results provide a mechanism which explains how the expression of an HLA-B27 molecule can impact the course of Salmonella infection and reactive arthritis.
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spelling pubmed-35499112013-01-24 Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells Ruuska, Marja Sahlberg, Anna S. Granfors, Kaisa Penttinen, Markus A. PLoS One Research Article A tissue antigen, HLA-B27, is strongly associated with a group of rheumatic diseases called spondyloarthritides. Despite the intensive research, the exact role of HLA-B27 in the pathogenesis of these diseases is still unclear. Here we studied whether HLA-B27 modulates the phosphorylation of signal transducer and activator of transcription 1 (STAT-1) serine 727 residue and the localization of STAT-1 in Salmonella-infected human monocytic cells. In addition, we studied the role of signaling molecule double-stranded RNA activated protein kinase (PKR) in these modulatory effects. U937 human monocytic cell transfectants stably expressing wild type HLA-B27 or mutated HLA-B27 heavy chains with amino acid substitutions in the B pocket were prepared. The PMA-differentiated cells were infected with S. enteritidis. Western blotting was used to detect the phosphorylation of STAT-1, and to visualize the localization of STAT-1 in the cells confocal microscopy was used. Specific inhibitors were employed to study the role of PKR in STAT-1 phosphorylation. We discovered that the phosphorylation of STAT-1 serine 727 is prolonged in cells expressing misfolding forms of HLA-B27 after S. enteritidis infection, whereas in mock cells and in cells expressing mutated, non-misfolding HLA-B27 the phosphorylation of serine 727 is transient. Interestingly, STAT-1 serine 727 phosphorylation is partly dependent on PKR. In addition, more STAT-1 is localized in the nucleus of HLA-B27-expressing cells, even before an external trigger, when compared to mock cells. In conclusion, our results show that the phosphorylation of STAT-1 serine 727 residue is prolonged in HLA-B27-expressing monocyte-macrophage U937 cells after bacterial infection. This is of interest since the phosphorylation of serine 727 on STAT-1 is suggested to contribute to macrophage activation and promote inflammatory responses. Therefore, our results provide a mechanism which explains how the expression of an HLA-B27 molecule can impact the course of Salmonella infection and reactive arthritis. Public Library of Science 2013-01-21 /pmc/articles/PMC3549911/ /pubmed/23349666 http://dx.doi.org/10.1371/journal.pone.0050684 Text en © 2013 Ruuska et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ruuska, Marja
Sahlberg, Anna S.
Granfors, Kaisa
Penttinen, Markus A.
Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells
title Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells
title_full Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells
title_fullStr Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells
title_full_unstemmed Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells
title_short Phosphorylation of STAT-1 Serine 727 Is Prolonged in HLA-B27-Expressing Human Monocytic Cells
title_sort phosphorylation of stat-1 serine 727 is prolonged in hla-b27-expressing human monocytic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549911/
https://www.ncbi.nlm.nih.gov/pubmed/23349666
http://dx.doi.org/10.1371/journal.pone.0050684
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