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.

Single-cell RNA-sequencing of Herpes simplex virus 1-infected cells identifies NRF2 activation as an antiviral program

“…Whereas SULF1 was previously shown to be induced by TNFα in MRC-5 fibroblasts [33], we found no clear activators for OXTR, but indications that proinflammatory cytokines such as IL-1β, IL-6, and TNFα might induce its transcription [34]. For the activation of NQO1 and the correlating genes FTH1, FTL, and SQSTM1, several reports pointed to the transcription factor NFE2L2 (also known as NRF2) [35][36][37].…”

Modulatory Mechanism of Polyphenols and Nrf2 Signaling Pathway in LPS Challenged Pregnancy Disorders

“…Prevalence of uterine inflammation is a major outcome of infection and idiopathic preterm birth [ 61 ] caused by alleviation of cytokine activity before preterm labor, cervix and fetal membranes by neutrophils and macrophages [ 62 ]. Several studies reported that proinflammatory cytokines such as IL-1 β , IL-6, and TNF- α may activate contraction-associated proteins (CAPs) comprising oxytocin receptor (OTR), connexin 43 (CX43), prostaglandin H synthase- (PGHS-) 2, and prostaglandin receptors, in the myometrium, which exert uterotonic factors such as PGs that induce subsequently labor and inflammatory signals, suggesting a potential target in attenuating preterm birth [ 63 ]. In addition, normal labor in mouse associates with subsequent stimulation of NF- κ B and AP-1 within the uterus, whereas LPS-induced preterm labor (PTL) in two mouse models has been reported to have activated NF- κ B and Jun N-terminal kinase (JNK) transcription factors [ 64 ].…”

Sulfur-containing gaseous signaling molecules

“…NaHS перешкоджає передчасним пологам у мишей, викликаним внутрішньоочеревинними ін'єкціямим ліпополісахариду. Цей протекторний ефект сірководню зумовлений пригніченням синтезу прозапальних цитокінів у біометрії [62]. Ферменти синтезу H 2 S наявні в епітелії піхви.…”