title: Hydrogen Sulfide Delays LPS-Induced Preterm Birth in Mice via Anti-Inflammatory Pathways.
abstract: A major cause of preterm labor in pregnant women is intra-amniotic infection, which is mediated by an inflammatory process. Hydrogen sulfide (H2S), a gaseous transmitter, has been implicated to be involved in inflammatory responses. We sought to investigate whether H2S affects infectious preterm birth using the mouse model of lipopolysaccharides (LPS)-induced preterm birth. Administration of LPS at 0.4 mg/kg with two injections intraperitoneally (i.p.) on gestational day 14.5 induced preterm labor. LPS significantly increased leukocyte infiltration in uterus, stimulated the expression of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), CCL2 and CXCL15 in myometrium. Administration of NaHS (i.p.) delayed the onset of labor induced by LPS in a dose-dependent manner. NaHS prevented leukocyte infiltration into intrauterine tissues and inhibited the production of pro-inflammatory cytokines in myometrium and decreased the levels of these cytokines in maternal circulation. H2S also decreased LPS-activated extracellular signal-regulated kinase (ERK) 1/2/ nuclear factor (NF)-κB signaling pathways in myometrium. This study provides new in vivo evidence for the roles of H2S in attenuating inflammation, and a potential novel therapeutic strategy for infection-related preterm labor.
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, China.
authors.forename: Xingji
authors.initials: X
authors.lastname: You
authors.affiliation: Departments of Obstetrics and Gynecology, Pediatrics and Physiology, University of Alberta, Edmonton, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Olson
authors.affiliation: Departments of Pediatrics, Ophthalmology and Pharmacology, CHU Sainte-Justine Research Centre, Montréal, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D007752:Obstetric Labor, Premature / Q000139:chemically induced*; D011247:Pregnancy
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D006862:Hydrogen Sulfide