69 Oxidative stress induces inflammatory response in placental explants: Immune and inflammatory mechanisms
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文摘
Oxidative stress arises from imbalance between generation of reactive oxygen species and anti-oxidant capacity of specific tissues. This alteration has been correlated with some disorders in pregnancy, mainly with pre-eclampsia (PE). In PE, placental oxidative stress contributes with the intense inflammatory response of the disease and supposed pathways related to this alteration include the formation of Inflammasome complexes that mediate the maturation of pro-inflammatory cytokines.

<h4 id="absSec_2">Objectivesh4>

This study aims to evaluate if the treatment of placental explants with hydrogen peroxide (H2O2) is able to induce inflammasome complexes in placentas from normotensive pregnant women and then increase inflammatory cytokines expression.

<h4 id="absSec_3">Methodsh4>

Placental explants were obtained from normotensive pregnant women undergoing elective cesarean section at 39 gestational weeks (N = 10). Placental explants were cultured in different concentrations of H2O2 (10, 100, 1000, 2000 and 10,000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M) for 4 h. Explant controls were cultured only supplemented medium. Gene expression for cytokines (IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh>, IL-10 and TNF-hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si3.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=ad7660aa9ef9ed0a8a41d1e7da7c68a8" title="Click to view the MathML source">α)hContainer hidden">hCode">h altimg="si3.gif" overflow="scroll">αhy="false">)h> and Caspase-1 were determined by RT-qPCR. Differences between groups were analyzed by non-parametric tests with significance level set at 5%.

<h4 id="absSec_4">Resultsh4>

Explants cultured with 1000, 2000 and 10,000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M of H2O2 showed lower IL-10 mRNA expression than controls. On the contrary, higher gene expression of TNF-hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si5.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=7e36cc5d846f61e969a232bce69ead92" title="Click to view the MathML source">αhContainer hidden">hCode">h altimg="si5.gif" overflow="scroll">hvariant="normal">αh> was observed in the same concentrations. Interestingly, IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh> mRNA expression was higher in the presence of 10 and 100 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M H2O2 concentrations than in 10,000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M. IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh> mRNA expression was also higher in cultures with 100 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M H2O2 concentration than in 1000 and 2000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M. Gene expression of Caspase-1 was increased in cultures with 100 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M of H2O2 concentration.

<h4 id="absSec_5">Conclusionh4>

These results suggest that the oxidative stress caused by H2O2 can activate caspase-1 wich participates in inflammasomes pathway and consequently increases the release of pro-inflammatory cytokines, such as IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh> and TNF-hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si5.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=7e36cc5d846f61e969a232bce69ead92" title="Click to view the MathML source">αhContainer hidden">hCode">h altimg="si5.gif" overflow="scroll">hvariant="normal">αh>. In addition, different responses among different concentrations of H2O2 raise the importance of the oxidative stress intensity for pathological process. Financial support &ndash; FAPESP 2014/25611-5.

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