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Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function
Multiple protozoans produce homologs of the cytokine MIF which play a role in immune evasion, invasion and pathogenesis. However, how parasite-encoded MIF activity is controlled remains poorly understood. Cytokine activity can be inhibited by intracellular binding partners that are released in the e...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035221/ https://www.ncbi.nlm.nih.gov/pubmed/29980718 http://dx.doi.org/10.1038/s41598-018-28625-1 |
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author | Ghosh, Swagata Leaton, Laura Ann Farr, Laura Barfield, Alexis Moonah, Shannon |
author_facet | Ghosh, Swagata Leaton, Laura Ann Farr, Laura Barfield, Alexis Moonah, Shannon |
author_sort | Ghosh, Swagata |
collection | PubMed |
description | Multiple protozoans produce homologs of the cytokine MIF which play a role in immune evasion, invasion and pathogenesis. However, how parasite-encoded MIF activity is controlled remains poorly understood. Cytokine activity can be inhibited by intracellular binding partners that are released in the extracellular space during cell death. We investigated the presence of an endogenous parasite protein that was capable of interacting and interfering with MIF activity. A screen for protein-protein interaction was performed using immunoaffinity purification of amebic cell lysate with specific anti-Entamoeba histolytica MIF (EhMIF) antibody followed by mass spectrometry analysis, which revealed an E. histolytica-produced JAB1 protein (EhJAB1) as a potential binding partner. JAB1 was found to be highly conserved in protozoans. Direct interaction between the EhMIF and EhJAB1 was confirmed by several independent approaches with GST pull-down, co-immunoprecipitation, and Biolayer interferometry (BLI) assays. Furthermore, the C-terminal region outside the functional JAMM deneddylase motif was required for EhMIF binding, which was consistent with the top in silico predictions. In addition, EhJAB1 binding blocked EhMIF-induced IL-8 production by human epithelial cells. We report the initial characterization of a parasite-encoded JAB1 and uncover a new binding partner for a protozoan-produced MIF protein, acting as a possible negative regulator of EhMIF. |
format | Online Article Text |
id | pubmed-6035221 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60352212018-07-12 Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function Ghosh, Swagata Leaton, Laura Ann Farr, Laura Barfield, Alexis Moonah, Shannon Sci Rep Article Multiple protozoans produce homologs of the cytokine MIF which play a role in immune evasion, invasion and pathogenesis. However, how parasite-encoded MIF activity is controlled remains poorly understood. Cytokine activity can be inhibited by intracellular binding partners that are released in the extracellular space during cell death. We investigated the presence of an endogenous parasite protein that was capable of interacting and interfering with MIF activity. A screen for protein-protein interaction was performed using immunoaffinity purification of amebic cell lysate with specific anti-Entamoeba histolytica MIF (EhMIF) antibody followed by mass spectrometry analysis, which revealed an E. histolytica-produced JAB1 protein (EhJAB1) as a potential binding partner. JAB1 was found to be highly conserved in protozoans. Direct interaction between the EhMIF and EhJAB1 was confirmed by several independent approaches with GST pull-down, co-immunoprecipitation, and Biolayer interferometry (BLI) assays. Furthermore, the C-terminal region outside the functional JAMM deneddylase motif was required for EhMIF binding, which was consistent with the top in silico predictions. In addition, EhJAB1 binding blocked EhMIF-induced IL-8 production by human epithelial cells. We report the initial characterization of a parasite-encoded JAB1 and uncover a new binding partner for a protozoan-produced MIF protein, acting as a possible negative regulator of EhMIF. Nature Publishing Group UK 2018-07-06 /pmc/articles/PMC6035221/ /pubmed/29980718 http://dx.doi.org/10.1038/s41598-018-28625-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ghosh, Swagata Leaton, Laura Ann Farr, Laura Barfield, Alexis Moonah, Shannon Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function |
title | Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function |
title_full | Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function |
title_fullStr | Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function |
title_full_unstemmed | Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function |
title_short | Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function |
title_sort | interaction between parasite-encoded jab1/csn5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035221/ https://www.ncbi.nlm.nih.gov/pubmed/29980718 http://dx.doi.org/10.1038/s41598-018-28625-1 |
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