Regulation of miRNA transcription in macrophages in response to Candida albicans.

Macrophages detect pathogens via pattern recognition receptors (PRRs), which trigger several intracellular signaling cascades including the MAPK and NFκB pathways. These in turn mediate the up-regulation of pro-inflammatory cytokines that are essential to combat the pathogen. However as the over-pro...

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Autores principales: Claire E Monk, György Hutvagner, J Simon C Arthur
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Publicado: Public Library of Science (PLoS) 2010
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Acceso en línea:https://doaj.org/article/fcea103586394e7291b0f56ca5444b7b
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spelling oai:doaj.org-article:fcea103586394e7291b0f56ca5444b7b2021-11-18T07:02:47ZRegulation of miRNA transcription in macrophages in response to Candida albicans.1932-620310.1371/journal.pone.0013669https://doaj.org/article/fcea103586394e7291b0f56ca5444b7b2010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21060679/?tool=EBIhttps://doaj.org/toc/1932-6203Macrophages detect pathogens via pattern recognition receptors (PRRs), which trigger several intracellular signaling cascades including the MAPK and NFκB pathways. These in turn mediate the up-regulation of pro-inflammatory cytokines that are essential to combat the pathogen. However as the over-production of pro-inflammatory cytokines results in tissue damage or septic shock, precise control of these signaling pathways is essential and achieved via the induction of multiple negative feedback mechanisms. miRNAs are small regulatory RNAs that are able to affect protein expression, via the regulation of either mRNA stability or translation. Up-regulation of specific miRNAs could have the potential to modulate PRR signaling, as has been shown for both miR-146 and miR-155. Here we have analysed which miRNAs are up-regulated in mouse macrophages in response to the fungal pathogen heat killed Candida albicans and compared the profile to that obtained with the TLR4 ligand LPS. We found that in addition to miR-146 and miR-155, both Candida albicans and LPS were also able to up-regulate miR-455 and miR-125a. Analysis of the signaling pathways required showed that NFκB was necessary for the transcription of all 4 pri-miRNAs, while the ERK1/2 and p38 MAPK pathways were also required for pri-miR-125a transcription. In addition the anti-inflammatory cytokine IL-10 was found to be able to induce miR-146a and b, but inhibited miR-155 induction. These results suggest that miR-455, miR-125, miR-146 and miR-155 may play important roles in regulating macrophage function following PRR stimulation.Claire E MonkGyörgy HutvagnerJ Simon C ArthurPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13669 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Claire E Monk
György Hutvagner
J Simon C Arthur
Regulation of miRNA transcription in macrophages in response to Candida albicans.
description Macrophages detect pathogens via pattern recognition receptors (PRRs), which trigger several intracellular signaling cascades including the MAPK and NFκB pathways. These in turn mediate the up-regulation of pro-inflammatory cytokines that are essential to combat the pathogen. However as the over-production of pro-inflammatory cytokines results in tissue damage or septic shock, precise control of these signaling pathways is essential and achieved via the induction of multiple negative feedback mechanisms. miRNAs are small regulatory RNAs that are able to affect protein expression, via the regulation of either mRNA stability or translation. Up-regulation of specific miRNAs could have the potential to modulate PRR signaling, as has been shown for both miR-146 and miR-155. Here we have analysed which miRNAs are up-regulated in mouse macrophages in response to the fungal pathogen heat killed Candida albicans and compared the profile to that obtained with the TLR4 ligand LPS. We found that in addition to miR-146 and miR-155, both Candida albicans and LPS were also able to up-regulate miR-455 and miR-125a. Analysis of the signaling pathways required showed that NFκB was necessary for the transcription of all 4 pri-miRNAs, while the ERK1/2 and p38 MAPK pathways were also required for pri-miR-125a transcription. In addition the anti-inflammatory cytokine IL-10 was found to be able to induce miR-146a and b, but inhibited miR-155 induction. These results suggest that miR-455, miR-125, miR-146 and miR-155 may play important roles in regulating macrophage function following PRR stimulation.
format article
author Claire E Monk
György Hutvagner
J Simon C Arthur
author_facet Claire E Monk
György Hutvagner
J Simon C Arthur
author_sort Claire E Monk
title Regulation of miRNA transcription in macrophages in response to Candida albicans.
title_short Regulation of miRNA transcription in macrophages in response to Candida albicans.
title_full Regulation of miRNA transcription in macrophages in response to Candida albicans.
title_fullStr Regulation of miRNA transcription in macrophages in response to Candida albicans.
title_full_unstemmed Regulation of miRNA transcription in macrophages in response to Candida albicans.
title_sort regulation of mirna transcription in macrophages in response to candida albicans.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/fcea103586394e7291b0f56ca5444b7b
work_keys_str_mv AT claireemonk regulationofmirnatranscriptioninmacrophagesinresponsetocandidaalbicans
AT gyorgyhutvagner regulationofmirnatranscriptioninmacrophagesinresponsetocandidaalbicans
AT jsimoncarthur regulationofmirnatranscriptioninmacrophagesinresponsetocandidaalbicans
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