Regulation of miRNA transcription in macrophages in response to candida albicans

Monk, CE; Hutvagner, G; Arthur, JSC

Regulation of miRNA transcription in macrophages in response to candida albicans

Monk, CE Hutvagner, G

Arthur, JSC

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2010, 5 (10)
Issue Date:: 2010-11-17

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Field	Value	Language
dc.contributor.author	Monk, CE	en_US
dc.contributor.author	Hutvagner, G https://orcid.org/0000-0002-7231-9446	en_US
dc.contributor.author	Arthur, JSC	en_US
dc.date.available	2010-09-21	en_US
dc.date.issued	2010-11-17	en_US
dc.identifier.citation	PLoS ONE, 2010, 5 (10)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/15291
dc.description.abstract	Macrophages detect pathogens via pattern recognition receptors (PRRS), which trigger several intracellular signaling cascades including the MAPK and NFKB 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 NFKB 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. © 2010 Monk et al.	en_US
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0013669	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Candida albicans	en_US
dc.subject.mesh	Lipopolysaccharides	en_US
dc.subject.mesh	NF-kappa B	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	DNA Primers	en_US
dc.subject.mesh	Interleukin-10	en_US
dc.subject.mesh	Oligonucleotide Array Sequence Analysis	en_US
dc.subject.mesh	Reverse Transcriptase Polymerase Chain Reaction	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	MAP Kinase Signaling System	en_US
dc.subject.mesh	Transcription, Genetic	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Base Sequence	en_US
dc.title	Regulation of miRNA transcription in macrophages in response to candida albicans	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	5	en_US
utslib.for	0903 Biomedical Engineering	en_US
dc.location.activity	ISI:000283537000037	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	5	en_US

Abstract:

Macrophages detect pathogens via pattern recognition receptors (PRRS), which trigger several intracellular signaling cascades including the MAPK and NFKB 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 NFKB 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. © 2010 Monk et al.

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http://hdl.handle.net/10453/15291