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Statements

Subject Item
n2:RIV%2F00216208%3A11310%2F14%3A10285598%21RIV15-MSM-11310___
rdf:type
n16:Vysledek skos:Concept
rdfs:seeAlso
http://dx.doi.org/10.1002/eji.201344040
dcterms:description
Mammalian TLRs in adult animals serve indispensable functions in establishing innate and adaptive immunity and contributing to the homeostasis of surrounding tissues. However, the expression and function of TLRs during mammalian embryonic development has not been studied so far. Here, we show that CD45(+) CD11b(+) F4/80(+) macrophages from 10.5-day embryo (E10.5) co-express TLRs and CD14. These macrophages, which have the capability to engulf both apoptotic cells and bacteria, secrete a broad spectrum of proinflammatory cytokines and chemokines upon TLR stimulation, demonstrating that their TLRs are functional. Comparative microarray analysis revealed an additional set of genes that were significantly upregulated in E10.5 TLR2(+) CD11b(+) macrophages. This analysis, together with our genetic, microscopic, and biochemical evidence, showed that embryonic phagocytes express protein machinery that is essential for the recycling of cellular iron and that this expression can be regulated by TLR engagement in a MyD88-dependent manner, leading to typical inflammatory M1 responses. These results characterize the utility of TLRs as suitable markers for early embryonic phagocytes as well as molecular triggers of cellular responses, the latter being demonstrated by the involvement of TLRs in an inflammation-mediated regulation of embryonic homeostasis via iron metabolism. Mammalian TLRs in adult animals serve indispensable functions in establishing innate and adaptive immunity and contributing to the homeostasis of surrounding tissues. However, the expression and function of TLRs during mammalian embryonic development has not been studied so far. Here, we show that CD45(+) CD11b(+) F4/80(+) macrophages from 10.5-day embryo (E10.5) co-express TLRs and CD14. These macrophages, which have the capability to engulf both apoptotic cells and bacteria, secrete a broad spectrum of proinflammatory cytokines and chemokines upon TLR stimulation, demonstrating that their TLRs are functional. Comparative microarray analysis revealed an additional set of genes that were significantly upregulated in E10.5 TLR2(+) CD11b(+) macrophages. This analysis, together with our genetic, microscopic, and biochemical evidence, showed that embryonic phagocytes express protein machinery that is essential for the recycling of cellular iron and that this expression can be regulated by TLR engagement in a MyD88-dependent manner, leading to typical inflammatory M1 responses. These results characterize the utility of TLRs as suitable markers for early embryonic phagocytes as well as molecular triggers of cellular responses, the latter being demonstrated by the involvement of TLRs in an inflammation-mediated regulation of embryonic homeostasis via iron metabolism.
dcterms:title
Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis
skos:prefLabel
Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis
skos:notation
RIV/00216208:11310/14:10285598!RIV15-MSM-11310___
n3:aktivita
n4:P n4:I n4:S
n3:aktivity
I, P(IAA500520707), S
n3:cisloPeriodika
5
n3:dodaniDat
n13:2015
n3:domaciTvurceVysledku
n5:7199384 n5:9703888 n5:1262343
n3:druhVysledku
n7:J
n3:duvernostUdaju
n19:S
n3:entitaPredkladatele
n14:predkladatel
n3:idSjednocenehoVysledku
50691
n3:idVysledku
RIV/00216208:11310/14:10285598
n3:jazykVysledku
n6:eng
n3:klicovaSlova
TLR stimulation; Iron metabolism; Gene expression microarray; Ferroportin; Embryonic macrophages
n3:klicoveSlovo
n10:Gene%20expression%20microarray n10:Ferroportin n10:Embryonic%20macrophages n10:Iron%20metabolism n10:TLR%20stimulation
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[9C1D64AEDE6A]
n3:nazevZdroje
European Journal of Immunology
n3:obor
n15:EC
n3:pocetDomacichTvurcuVysledku
3
n3:pocetTvurcuVysledku
6
n3:projekt
n17:IAA500520707
n3:rokUplatneniVysledku
n13:2014
n3:svazekPeriodika
44
n3:tvurceVysledku
Balounová, Jana Benesova, Martina Ballek, Ondřej Filipp, Dominik Vavrochová, Tereza Kolar, Michal
n3:wos
000335003200024
s:issn
0014-2980
s:numberOfPages
12
n8:doi
10.1002/eji.201344040
n18:organizacniJednotka
11310