Cervical Gene Delivery of the Antimicrobial Peptide, Human β-Defensin (HBD)-3, in a Mouse Model of Ascending Infection-Related Preterm Birth

Suff, Natalie; Karda, Rajvinder; Díaz, Juan Antinao; Ng, Joanne; Baruteau, Julien; Perocheau, Dany; Taylor, Peter W.; Alber, Dagmar; Buckley, Suzanne M.K.; Bajaj‐Elliott, Mona; Waddington, Simon; Peebles, Donald

doi:10.3389/fimmu.2020.00106

Cited by 22 publications

(14 citation statements)

References 72 publications

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“…The incidence of preterm birth (PTB) is about 5%‐18%, but it causes 85% of neonatal death 1,2 . Intrauterine infection is a major cause of preterm delivery, accounting for 40% of all PTB cases worldwide 3,4 . Chorioamnionitis (CAM) is a common complication of pregnancy, which is the leading cause of premature delivery, stillbirth, neonatal infection and septicaemia worldwide 5 .…”

Section: Introductionmentioning

confidence: 99%

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis

Zhang

et al. 2020

J Cellular Molecular Medi

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Chorioamnionitis (CAM), as a common intrauterine infectious disease, is the leading cause of premature birth, stillbirth, neonatal infection and sepsis. The formyl peptide receptor 2 (FPR2) is a member of GPCRs widely distributed in a variety of tissues and is associated with many inflammatory diseases. With the discovery of FPR2 in human placenta, the possibility of exploring the function of FPR2 in obstetrics is evolving. The Resolvin D1 (RvD1) plays an important role in the resolution of inflammation by combining with FPR2. In this study, we evaluated the role of FPR2 and RvD1 in CAM, not only in the human placenta but also in mouse models. The expression of FPR2 increased in the placenta of CAM patients and the downstream PPARγ/NF‐κB signalling changed accordingly. Moreover, Fpr2−/− mice were highly susceptible to LPS, displaying a worse CAM symptom, compared with WT mice. By establishing a model of trophoblast inflammation in vitro, it was confirmed that RvD1 rescued the effect of LPS on inflammation by combining with FPR2 and its downstream PPARγ/NF‐κB pathway. Otherwise, RvD1 improved the preterm labour in a mouse model of CAM induced by LPS. Altogether, these findings show that RvD1 alleviated the inflammation of trophoblast in vivo and in vitro through FPR2/PPARγ/NF‐κB pathway, suggesting RvD1/FPR2 might be a novel therapeutic strategy to alleviate CAM.

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Section: Introductionmentioning

confidence: 99%

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis

Zhang

et al. 2020

J Cellular Molecular Medi

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“…On the other hand, a lower level of hBD-2 was reported by Kotani et al [ 36 ] in the first trimester of pregnancy in BV-positive women. Experimental data inducing cervical hBD-3 gene expression in a mouse model of ascending infection-related preterm birth demonstrated that hBD-3 reduces microbial ascension into the pregnant uterine cavity, reducing the frequency of premature deliveries [ 37 ]. These findings reinforce that hBDs may be potential candidates for augmenting cervical innate immunity, to prevent ascending infection and to reduce susceptibility to sexually transmitted infections, which is supported by the observations that antimicrobial activity is increased in samples with higher hBD-2 concentrations [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Cervicovaginal levels of human beta defensins during bacterial vaginosis

et al. 2021

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Aims To compare the cervicovaginal levels of human beta defensin (hBD)-1, 2 and 3 of women according to the status of Nugent-defined bacterial vaginosis (BV). Methods A total of 634 women of reproductive age were included in the study. Participants were equally distributed in two groups: according to the classification of vaginal smears according to Nugent criteria in normal (scores 0 to 3) and BV (scores ≥7). Cervicovaginal fluid samples were used for measurements of hBDs1, 2 and 3 levels by enzyme-linked immunosorbent assay (ELISA). Levels of each hBD were compared between the two study groups using Mann-Whitney test, with p-value <0.05 considered as significant. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for sociodemographic variables and hBD1-3 levels associated with BV a multivariable analysis. Correlation between Nugent score and measured levels of hBDs1-3 were calculated using Spearman’s test. Results Cervicovaginal fluids from women with BV showed lower levels of hBD-1 [median 2,400.00 pg/mL (0–27,800.00); p<0.0001], hBD-2 [5,600.00 pg/mL (0–45,800.00); p<0.0001] and hBD-3 [1,600.00 pg/mL (0–81,700.00); p = 0.012] when compared to optimal microbiota [hBD-1: [median 3,400.00 pg/mL (0–35,600.00), hBD-2: 12,300.00 pg/mL (0–95,300.00) and hBD-3: 3,000.00 pg/mL (0–64,300.00), respectively]. Multivariable analysis showed that lower levels of hBD-1 (OR: 2.05; 95% CI: 1.46–2.87), hBD-2 (OR: 1.85; 95% CI: 1.32–2.60) and hBD-3 (OR: 1.90; 95% CI: 1.37–2.64) were independently associated BV. Significant negative correlations were observed between Nugent scores and cervicovaginal levels of hBD-1 (Spearman’s rho = -0.2118; p = 0.0001) and hBD-2 (*Spearman’s rho = -0.2117; p = 0.0001). Conclusions Bacterial vaginosis is associated with lower cervicovaginal levels of hBDs1-3 in reproductive-aged women.

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“…In COVID-19, a lower dosage than the MTD (as well as the subcutaneous route for interferon beta) can be therapeutically effective only if synergistic effects are utilized, i.e., if interferon is used in combination with other antiviral agents, as demonstrated in some recent clinical studies ( 13 – 16 ). Furthermore, relatively low doses can successfully be employed without concomitant administration of other antivirals if interferon is given by inhalation ( 17 , 18 ). However, interferon applied by this route will probably act on the (upper) respiratory tract only but not on other organs, which are frequently infected by SARS-CoV-2, too, especially in severe cases of COVID-19.…”

Section: Dosages To Be Used With Interferons In Covid-19mentioning

confidence: 99%