Preeclampsia (PE) is a preg
na
ncy disorder characterized by a
n imbala
nce betwee
n pro- a
nd a
nti-i
nflammatory cytoki
nes associated with high plasma levels of uric acid a
nd I
nterleuki
n-1 beta (IL-1
n id="mmlsi1" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si1.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=2b73ccb09d67690cab9eaeb3054dbb9f" title="Click to view the MathML source">β)n>n class="mathContainer hidden">n class="mathCode">n>n>n> i
n the severe cases of PE. Uric acid acts as a da
nger-associated molecular patter
n (DAMP) a
nd activates the i
nflammasome i
n the trophoblast cells, leadi
ng to IL-1
n id="mmlsi2" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si2.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=f3934d1c73ab33293fb83619fd0019f2" title="Click to view the MathML source">βn>n class="mathContainer hidden">n class="mathCode">n>n>n> secretio
n. I
nflammasomes are i
ntracellular multiprotei
n complexes which mediate i
nnate immu
ne respo
nse via caspase-1 activatio
n, resulti
ng i
n IL-1
n id="mmlsi2" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si2.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=f3934d1c73ab33293fb83619fd0019f2" title="Click to view the MathML source">βn>n class="mathContainer hidden">n class="mathCode">n>n>n> a
nd IL-18 secretio
n i
n their active forms.
Objectives
As placenta seems to play an important role in the pathogenesis of PE the present study aimed to investigate the expression of gene and proteins related to the inflammasome in placenta from preeclamptic women.
Methods
Placental tissue was collected from 20 normotensive pregnant women and 20 preeclamptic women, and NLRP3, caspase-1, IL-1n id="mmlsi2" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si2.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=f3934d1c73ab33293fb83619fd0019f2" title="Click to view the MathML source">βn>n class="mathContainer hidden">n class="mathCode">n>n>n>, tumor necrosis factor-alpha (TNF-n id="mmlsi5" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si5.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=a422dcfcfc95640161e4e70e3a70a2c8" title="Click to view the MathML source">α)n>n class="mathContainer hidden">n class="mathCode">n>n>n>, IL-18 and high-mobility group box 1 protein (HMGB1) were evaluated by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and also analyzed by quantitative real-time polymerase chain reaction (RT-qPCR).
Results
Placenta from pregnant women with PE showed increased mRNA expression for NLRP3, caspase-1, IL-1n id="mmlsi2" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si2.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=f3934d1c73ab33293fb83619fd0019f2" title="Click to view the MathML source">βn>n class="mathContainer hidden">n class="mathCode">n>n>n> and TNF-n id="mmlsi7" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si7.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=05de2d1ea11da339b15b9f8fc70edc56" title="Click to view the MathML source">αn>n class="mathContainer hidden">n class="mathCode">n>n>n> as well as their protein expression. Higher levels of caspase 1, IL-1n id="mmlsi2" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si2.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=f3934d1c73ab33293fb83619fd0019f2" title="Click to view the MathML source">βn>n class="mathContainer hidden">n class="mathCode">n>n>n> and TNF-n id="mmlsi7" class="mathmlsrc">n class="formulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916301799&_mathId=si7.gif&_user=111111111&_pii=S2210778916301799&_rdoc=1&_issn=22107789&md5=05de2d1ea11da339b15b9f8fc70edc56" title="Click to view the MathML source">αn>n class="mathContainer hidden">n class="mathCode">n>n>n> were detected by ELISA in placental homogenate of preeclamptic group than in normotensive group. Lower expression of mRNA for IL-18 and its protein expression were detected in placenta of pregnant women with PE compared with normotensive group. No significant differences were observed between control and preeclamptic groups in relation to HMGB1 gene and protein expression.
Conclusion
The results suggest that placenta from pregnant women with preeclampsia shows activation of NLRP3 inflammasome which may be involved in the exaggerated inflammatory state detected in women with preeclampsia.
Financial support: Fapesp 2012/24697-8 and 2013/00535-1