Prevention of lipopolysaccharide-induced preterm labor by the lack of CX3CL1-CX3CR1 interaction in mice

Abstract

Preterm labor (PTL) is the most common cause of neonatal death and long-term adverse outcome. The pharmacological agents for PTL prevention are palliative and frequently fail to prevent PTL and improve neonatal outcome. It is essential to fully understand the molecular mechanisms of PTL in order to develop novel therapeutic methods against PTL. Several lines of evidence indicate some chemokines are expressed in gestational tissues during labor or PTL. To reveal the pathophysiological roles of the CX3CL1-CX3CR1 axis in PTL, we performed present study using LPS-induced PTL mice model in CX3CR1-deficient (Cx3cr1-/-) mice. We indicated that PTL was suppressed in Cx3cr1-/- mice and immunoneutralization of CX3CL1 in WT mice. From immunohistochemical and the gene expression analyses, the CX3CL1-CX3CR1 axis has detrimental roles in PTL through intrauterine recruitment of macrophages and the enhancement of macrophage-derived inflammatory mediators. Thus, the CX3CL1-CX3CR1 axis may be a good molecular target for preventing PTL.

Cytokine profiles of umbilical cord blood mononuclear cells upon in vitro stimulation with lipopolysaccharides of different vaginal gram-negative bacteria

“…LPS-mediated inflammatory response is clearly correlated to prematurity or fetal loss [39–42]. A role of the CX3CL1-CX3CR1 chemokine signaling pathway through intrauterine recruitment of macrophages and the enhancement of macrophage-derived inflammatory mediators was recently demonstrated in LPS-induced PTL in mice [43].…”

IL-27 Mediates Neutrophils Infiltration at the Maternal and Fetal Interface in Preterm Labor With Infection

“…Indeed, IL-27R signaling contributed to Ly6G + neutrophils accumulation in diseased aorta of mice model with aortic aneurysm [24]. Our previous work had suggested that IL-27 can promote the in ammatory process of human FMs in preterm labor [17]. Therefore,we speculated that IL-27 could contribute to the increased in ammation by affecting neutrophils in ltration at the maternal and fetal interface.…”

“…The vaginal plugs were checked the next morning, whose presence indicated gestational day of 0.5. The mice model of PTLI was established as previously reported [16,17]. Brie y, at gestational day of 16.5, the pregnant mice were intraperitoneally administered with LPS (25μg in 200μl PBS) or PBS 200μl.…”

A Broad-Spectrum Chemokine Inhibitor Blocks Inflammation-Induced Myometrial Myocyte–Macrophage Crosstalk and Myometrial Contraction

“…Furthermore, compared to women not in labour, women at term in labour or women in PTL display a high density of tissue resident macrophages [ 36 ]. Most significantly, it has been shown that macrophage depletion in a rodent model prevents infection-induced PTL [ 37 , 38 ] and cervical remodelling [ 38 , 39 ].…”