title: 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.
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.
authors.affiliation: Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ozlem.equils@cshs.org
authors.forename: Ozlem
authors.initials: O
authors.lastname: Equils
authors.forename: Chantelle
authors.initials: C
authors.lastname: Moffatt-Blue
authors.forename: Tomo-o
authors.initials: TO
authors.lastname: Ishikawa
authors.forename: Charles F
authors.initials: CF
authors.lastname: Simmons
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ilievski
authors.forename: Emmet
authors.initials: E
authors.lastname: Hirsch
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002154:Calpain / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005321:Extraembryonic Membranes / Q000378:metabolism / Q000382:microbiology; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D006080:Ovarian Follicle / Q000378:metabolism / Q000382:microbiology; D010920:Placenta / Q000378:metabolism / Q000382:microbiology; D011247:Pregnancy; D047928:Premature Birth / Q000201:enzymology / Q000382:microbiology* / Q000517:prevention & control*; D013290:Streptococcal Infections / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000502:physiology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D002154:Calpain; D020169:Caspases