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Pretreatment with pancaspase inhibitor (Z-VAD-FMK) delays but does not prevent intraperitoneal heat-killed group B Streptococcus-induced preterm delivery in a pregnant mouse model.

Equils O, Moffatt-Blue C, Ishikawa TO, Simmons CF, Ilievski V, Hirsch E - Infect Dis Obstet Gynecol (2009)

Bottom Line: Objective.The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ozlem.equils@cshs.org

ABSTRACT
Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis. Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery. Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS). Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection. Results. Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery. Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

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Intrauterine HK-GBS injection induces placental m-calpain expression in a time-dependent manner. Day 14.5 pregnant mice were euthanized 14 hours after exposure to PBS (i) or HK-GBS (ii). Placentas were removed and stained for m-calpain. Data from a representative of three separate experiments is shown.
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fig5: Intrauterine HK-GBS injection induces placental m-calpain expression in a time-dependent manner. Day 14.5 pregnant mice were euthanized 14 hours after exposure to PBS (i) or HK-GBS (ii). Placentas were removed and stained for m-calpain. Data from a representative of three separate experiments is shown.

Mentions: We examined the effect of HK-GBS treatment on placental calpain expression and observed that i.u. HK-GBS injection led to a time-dependent increase in m-calpain expression in the mouse placenta within 14 hours of exposure as assessed by immunohistochemistry (Figure 5).


Pretreatment with pancaspase inhibitor (Z-VAD-FMK) delays but does not prevent intraperitoneal heat-killed group B Streptococcus-induced preterm delivery in a pregnant mouse model.

Equils O, Moffatt-Blue C, Ishikawa TO, Simmons CF, Ilievski V, Hirsch E - Infect Dis Obstet Gynecol (2009)

Intrauterine HK-GBS injection induces placental m-calpain expression in a time-dependent manner. Day 14.5 pregnant mice were euthanized 14 hours after exposure to PBS (i) or HK-GBS (ii). Placentas were removed and stained for m-calpain. Data from a representative of three separate experiments is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801448&req=5

fig5: Intrauterine HK-GBS injection induces placental m-calpain expression in a time-dependent manner. Day 14.5 pregnant mice were euthanized 14 hours after exposure to PBS (i) or HK-GBS (ii). Placentas were removed and stained for m-calpain. Data from a representative of three separate experiments is shown.
Mentions: We examined the effect of HK-GBS treatment on placental calpain expression and observed that i.u. HK-GBS injection led to a time-dependent increase in m-calpain expression in the mouse placenta within 14 hours of exposure as assessed by immunohistochemistry (Figure 5).

Bottom Line: Objective.The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ozlem.equils@cshs.org

ABSTRACT
Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis. Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery. Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS). Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection. Results. Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery. Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

Show MeSH
Related in: MedlinePlus