Recombinant human lactoferrin inhibits matrix metalloproteinase (MMP‐2, MMP‐3, and MMP‐9) activity in a rabbit preterm delivery model

Nakayama, K; Otsuki, Katsufumi; Yakuwa, Kyoko; Hasegawa, Akitoshi; Sawada, Masamichi; Mitsukawa, Kaori; Chiba, Hiroshi; Nagatsuka, Masaaki; Okai, Takashi

doi:10.1111/j.1447-0756.2008.00827.x

Cited by 12 publications

(8 citation statements)

References 26 publications

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“…Accordingly, levels of MMP3 have been reported to be increased at labour (28). Furthermore, LPS treatment increased MMP3 levels in human cervical smooth-muscle cells (29) and rabbit cervical tissues (30). In the present study, maternal administration of H 2 did not significantly decrease LPS-induced Mmp3 mRNA expression levels.…”

Section: Discussionsupporting

confidence: 44%

Effect of molecular hydrogen on uterine inflammation during preterm labour

et al. 2018

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Abstract. Intrauterine inflammation causes preterm birth and is associated with complications in preterm neonates. Thus, strategies aimed at suppressing inflammation are expected to be effective for reducing the risk of preterm birth and associated complications. Our previous studies demonstrated that molecular hydrogen (H 2 ), an anti-inflammatory agent, prevented inflammation-induced impairment in foetal brain and lung tissues in lipopolysaccharide (LPS)-induced rodent models. However, it remains unclear whether H 2 is capable of inhibiting preterm labour. The aim of the current study was therefore to investigate the effect of H 2 on inflammation-induced preterm labour. Pregnant ICR (CD-1) mice were divided into three groups: Control, LPS and H 2 water (HW) + LPS. In the control and LPS groups, vehicle and LPS, respectively, were intraperitoneally injected on embryonic day 15.5. In the HW + LPS group, HW was administered 24 h prior to LPS injection. The time from LPS administration to parturition was compared between the LPS and HW + LPS groups. Maternal uterus was collected 6 h after LPS injection and the transcript levels of pro-inflammatory cytokines, contractile-associated proteins (CAPs), matrix metalloproteinase-3 (Mmp3) and endothelin-1 (Et1)were assessed by reverse transcription-quantitative polymerase chain reaction. The protein levels of cyclooxygenase-2 (Cox2) were also evaluated by immunohistochemistry. The time from LPS administration to parturition in the HW + LPS group was significantly increased compared with that in the LPS group (33.5±3.4 vs. 18.3±8.8 h, respectively, P=0.020). H 2 administration also resulted in significantly higher progesterone levels compared with LPS treatment alone (P=0.002). The transcript levels of pro-inflammatory cytokines, CAPs, Mmp3 and Et1 in the uteri of the LPS group were significantly higher than those in the control group (all P<0.05). In turn, all these levels with the exception of interleukin-8 and Mmp3 were significantly lower in the HW + LPS group compared with those in the LPS group (all P<0.05). The protein levels of Cox2 in the LPS group were also significantly increased compared with those in the control (P<0.001) and HW + LPS (P= 0.003) groups. These results suggest that inflammation-induced changes in the uterus may be ameliorated through maternal H 2 administration. Preventive H 2 administration may therefore represent an effective strategy for the suppression of inflammation during preterm labour.

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Section: Discussionsupporting

confidence: 44%

Effect of molecular hydrogen on uterine inflammation during preterm labour

et al. 2018

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“…The LF extended the gestational periods and decreased the fetal mortality rate in the E. coli ‐administrated rabbit preterm delivery models, and also inhibited the production of TNF‐α, which is an inflammatory cytokine, in the maternal serum and the amniotic fluid . LF also inhibited cervical maturation in animal preterm delivery models . These results suggested the possibility that LF could be applied as a means for preventing and treating preterm delivery as well as improving the prognosis of newborns .…”

Section: Discussionmentioning

confidence: 81%

Administration of oral and vaginal prebiotic lactoferrin for a woman with a refractory vaginitis recurring preterm delivery: Appearance of lactobacillus in vaginal flora followed by term delivery

Otsuki

Tokunaka

Oba

et al. 2013

J of Obstet and Gynaecol

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Lactoferrin (LF) is one of the prebiotics present in the human body. A 38-year-old multiparous woman with poor obstetrical histories, three consecutive preterm premature rupture of membrane at the 19th, 23rd and 25th week of pregnancy, was referred to our hospital. She was diagnosed as having refractory vaginitis. Although estriol vaginal tablets were used for 4 months, the vaginitis was not cured. We administrated vaginal tablets and oral agents of prebiotic LF, resulting in a Lactobacillus predominant vaginal flora. When she was pregnant, she continued to use the LF, and the Lactobacillus in the vaginal flora was continuously observed during pregnancy. An elective cesarean section was performed at the 38th week of pregnancy. When the administration of LF was discontinued after the delivery, Lactobacillus in the vaginal flora was disappeared.

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“…Moreover, the inhibitory activity of apoLf against matrix metalloproteinase-2 (MMP-2) during involution suggests that this protein can be ascribed to a novel regulatory mechanism that regulates proteolysis by MMP-2 in vivo (Newsome et al 2007). The inhibition of MMP expression by recombinant human Lf has also been observed in a rabbit preterm delivery model, suggesting that the protein inhibits cervical maturation mediated by MMP activity (Nakayama et al 2008). In addition to its protective functions, an in vitro study of primary bovine mammary epithelial cells has suggested that Lf is involved in assisting the involution process by decreasing casein expression and reducing cell viability (Riley et al 2008).…”

Section: Discussionmentioning

confidence: 91%

Lactoferrin at basal side of mouse mammary epithelium derives in part from stroma cells

Pecorini¹,

Delpal²,

Truchet³

et al. 2009

Cell Tissue Res

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Lactoferrin is synthesized by glandular epithelial cells and neutrophils and is also present on both sides of the mammary epithelium. We have studied the origin of lactoferrin detected in the various compartments of mouse mammary tissue. As revealed by immunogold electron microscopy, lactoferrin is present in mammary epithelial cells and in the basal region of the epithelium, associated with connective tissue and stroma cells at all physiological stages studied. A perturbation of protein synthesis or transport after in vitro treatment with cycloheximide or brefeldin A does not abrogate lactoferrin labelling in the basal region of the epithelium. The expression of lactoferrin has also been observed in the fat pads of mammary glands from mice surgically depleted of epithelial cells. The sealing of one teat for 24 h is accompanied by an increase in both the number of stroma cells and the labelling of myoepithelial cells. Thus, the lactoferrin present in the interstitial space of the mouse mammary epithelium originates in part from stroma cells. Possible roles of lactoferrin at the basal side of the mammary epithelium are discussed.

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Recombinant human lactoferrin inhibits matrix metalloproteinase (MMP‐2, MMP‐3, and MMP‐9) activity in a rabbit preterm delivery model

Abstract: These results suggest that the prevention of preterm delivery by rh-LF in a rabbit model has been achieved through inhibition of cervical maturation promoted by matrix metalloproteinase activity.

Cited by 12 publications

References 26 publications

Effect of molecular hydrogen on uterine inflammation during preterm labour

Effect of molecular hydrogen on uterine inflammation during preterm labour

Administration of oral and vaginal prebiotic lactoferrin for a woman with a refractory vaginitis recurring preterm delivery: Appearance of lactobacillus in vaginal flora followed by term delivery

Lactoferrin at basal side of mouse mammary epithelium derives in part from stroma cells

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