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Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells

A prominent histopathological feature of Sjögren's syndrome, an autoimmune disease, is the presence of lymphocytic infiltrates in the salivary and lachrymal glands. Such infiltrates are comprised of activated lymphocytes and macrophages, and known to produce multiple cytokines including interfe...

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Autores principales: Arellano-Garcia, Martha E., Misuno, Kaori, Tran, Simon D., Hu, Shen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125149/
https://www.ncbi.nlm.nih.gov/pubmed/25102056
http://dx.doi.org/10.1371/journal.pone.0102878
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author Arellano-Garcia, Martha E.
Misuno, Kaori
Tran, Simon D.
Hu, Shen
author_facet Arellano-Garcia, Martha E.
Misuno, Kaori
Tran, Simon D.
Hu, Shen
author_sort Arellano-Garcia, Martha E.
collection PubMed
description A prominent histopathological feature of Sjögren's syndrome, an autoimmune disease, is the presence of lymphocytic infiltrates in the salivary and lachrymal glands. Such infiltrates are comprised of activated lymphocytes and macrophages, and known to produce multiple cytokines including interferon-gamma (IFN-γ). In this study, we have demonstrated that IFN-γ strongly induces the expression of immunoproteasome beta subunits (β1i, β2i and β5i) and immunoproteasome activity but conversely inhibits the expression of proteasome beta subunits (β1, β2 and β5) in human salivary gland (HSG) cells. Mass spectrometric analysis has revealed potential MHC I-associated peptides on the HSG cells, including a tryptic peptide derived from salivary amylase, due to IFN-γ stimulation. These results suggest that IFN-γ induces immunoproteasomes in HSG cells, leading to enhanced presentation of MHC I-associated peptides on cell surface. These peptide-presenting salivary gland cells may be recognized and targeted by auto-reactive T lymphocytes. We have also found that lactacystin, a proteasome inhibitor, inhibits the expression of β1 subunit in HSG cells and blocks the IFN-γ-induced expression of β1i and immunoproteasome activity. However, the expression of β2i and β5i in HSG cells is not affected by lactacystin. These results may add new insight into the mechanism regarding how lactacystin blocks the action of proteasomes or immunoproteasomes.
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spelling pubmed-41251492014-08-12 Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells Arellano-Garcia, Martha E. Misuno, Kaori Tran, Simon D. Hu, Shen PLoS One Research Article A prominent histopathological feature of Sjögren's syndrome, an autoimmune disease, is the presence of lymphocytic infiltrates in the salivary and lachrymal glands. Such infiltrates are comprised of activated lymphocytes and macrophages, and known to produce multiple cytokines including interferon-gamma (IFN-γ). In this study, we have demonstrated that IFN-γ strongly induces the expression of immunoproteasome beta subunits (β1i, β2i and β5i) and immunoproteasome activity but conversely inhibits the expression of proteasome beta subunits (β1, β2 and β5) in human salivary gland (HSG) cells. Mass spectrometric analysis has revealed potential MHC I-associated peptides on the HSG cells, including a tryptic peptide derived from salivary amylase, due to IFN-γ stimulation. These results suggest that IFN-γ induces immunoproteasomes in HSG cells, leading to enhanced presentation of MHC I-associated peptides on cell surface. These peptide-presenting salivary gland cells may be recognized and targeted by auto-reactive T lymphocytes. We have also found that lactacystin, a proteasome inhibitor, inhibits the expression of β1 subunit in HSG cells and blocks the IFN-γ-induced expression of β1i and immunoproteasome activity. However, the expression of β2i and β5i in HSG cells is not affected by lactacystin. These results may add new insight into the mechanism regarding how lactacystin blocks the action of proteasomes or immunoproteasomes. Public Library of Science 2014-08-07 /pmc/articles/PMC4125149/ /pubmed/25102056 http://dx.doi.org/10.1371/journal.pone.0102878 Text en © 2014 Arellano-Garcia 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
Arellano-Garcia, Martha E.
Misuno, Kaori
Tran, Simon D.
Hu, Shen
Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells
title Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells
title_full Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells
title_fullStr Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells
title_full_unstemmed Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells
title_short Interferon-γ Induces Immunoproteasomes and the Presentation of MHC I-Associated Peptides on Human Salivary Gland Cells
title_sort interferon-γ induces immunoproteasomes and the presentation of mhc i-associated peptides on human salivary gland cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125149/
https://www.ncbi.nlm.nih.gov/pubmed/25102056
http://dx.doi.org/10.1371/journal.pone.0102878
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