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Human cathelicidin production by the cervix.

Frew L, Makieva S, McKinlay AT, McHugh BJ, Doust A, Norman JE, Davidson DJ, Stock SJ - PLoS ONE (2014)

Bottom Line: The aim of this study was to investigate cathelicidin production, regulation and function in the cervix. hCAP18/LL-37 was found to be present in cervicovaginal secretions collected from women in the first trimester of pregnancy and to be expressed at significantly higher levels in samples from women with alterations in vaginal bacterial flora characteristic of bacterial vaginosis.However, no association was found between serum levels of vitamin D and hCAP18/LL-37 concentrations in cervicovaginal secretions (n = 116).Further investigation will elucidate the effects of hCAP18/LL-37 on the physiology and pathophysiology of labour, and may lead to strategies for the prevention of infection-associated preterm birth.

View Article: PubMed Central - PubMed

Affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
hCAP18/LL-37 is the sole human cathelicidin; a family of host defence peptides with key roles in innate host defence. hCAP18/LL-37 is expressed primarily by neutrophils and epithelial cells, but its production and function in the lower genital tract is largely uncharacterised. Despite the significant roles for cathelicidin in multiple organs and inflammatory processes, its impact on infections that could compromise fertility and pregnancy is unknown. The aim of this study was to investigate cathelicidin production, regulation and function in the cervix. hCAP18/LL-37 was found to be present in cervicovaginal secretions collected from women in the first trimester of pregnancy and to be expressed at significantly higher levels in samples from women with alterations in vaginal bacterial flora characteristic of bacterial vaginosis. In endocervical epithelial cell lines, expression of the gene encoding hCAP18/LL-37 (CAMP) was not affected by TLR agonists, but was found to be up-regulated by both 1, 25 hydroxyvitamin D3 and 25 hydroxyvitamin D3. However, no association was found between serum levels of vitamin D and hCAP18/LL-37 concentrations in cervicovaginal secretions (n = 116). Exposure to synthetic LL-37 had a pro-inflammatory effect on endocervical epithelial cell lines, increasing secretion of inflammatory cytokine IL-8. Together these data demonstrate inducible expression of hCAP18/LL-37 in the female lower reproductive tract in vivo and suggest the capacity for this peptide to modulate host defence to infection in this system. Further investigation will elucidate the effects of hCAP18/LL-37 on the physiology and pathophysiology of labour, and may lead to strategies for the prevention of infection-associated preterm birth.

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Effect of 25(OH) vitamin D3 on CYP27B1 expression in endocervical (END E6/E7) and ectocervical (ECT E6/E7) cell lines.Cells treated for 24(control), 3 nM, 30 nM or 100 nM 25(OH) vitamin D3. (A) End E6/E7 cells (n = 3), (B) Ect E6/E7 cells (n = 3). Data presented as mean fold change relative to control ± SEM (error bars). *, **, **, p<0.05, 0.01, 0.001 respectively compared with control (One-way ANOVA with Dunnett's post-test).
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pone-0103434-g005: Effect of 25(OH) vitamin D3 on CYP27B1 expression in endocervical (END E6/E7) and ectocervical (ECT E6/E7) cell lines.Cells treated for 24(control), 3 nM, 30 nM or 100 nM 25(OH) vitamin D3. (A) End E6/E7 cells (n = 3), (B) Ect E6/E7 cells (n = 3). Data presented as mean fold change relative to control ± SEM (error bars). *, **, **, p<0.05, 0.01, 0.001 respectively compared with control (One-way ANOVA with Dunnett's post-test).

Mentions: Treatment with TLR agonists; Pam3CSK (TLR 1/2 agonist), POLY (I:C) (TLR 3 agonist), Rec FLA-ST (TLR 5 agonist) and FSL-1 (TLR 2/6 agonist), had no effect on CAMP expression in END E6/E7 and ECT E6/E7 cells compared to untreated controls, but markedly up-regulated expression of DEFB4 (Figure 3). In contrast, treatment with 25(OH) vitamin D3 and 1, 25(OH) vitamin D3 up-regulated the expression of CAMP, but not DEFB4 in END E6/E7 and ECT E6/E7 cell lines (Figure 4). Treatment with 25(OH) vitamin D3 also increased the expression of the gene encoding 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) which catalyses the conversion of 25(OH) vitamin D3 to 1, 25(OH) vitamin D3 in each cell line (Figure 5).


Human cathelicidin production by the cervix.

Frew L, Makieva S, McKinlay AT, McHugh BJ, Doust A, Norman JE, Davidson DJ, Stock SJ - PLoS ONE (2014)

Effect of 25(OH) vitamin D3 on CYP27B1 expression in endocervical (END E6/E7) and ectocervical (ECT E6/E7) cell lines.Cells treated for 24(control), 3 nM, 30 nM or 100 nM 25(OH) vitamin D3. (A) End E6/E7 cells (n = 3), (B) Ect E6/E7 cells (n = 3). Data presented as mean fold change relative to control ± SEM (error bars). *, **, **, p<0.05, 0.01, 0.001 respectively compared with control (One-way ANOVA with Dunnett's post-test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4121085&req=5

pone-0103434-g005: Effect of 25(OH) vitamin D3 on CYP27B1 expression in endocervical (END E6/E7) and ectocervical (ECT E6/E7) cell lines.Cells treated for 24(control), 3 nM, 30 nM or 100 nM 25(OH) vitamin D3. (A) End E6/E7 cells (n = 3), (B) Ect E6/E7 cells (n = 3). Data presented as mean fold change relative to control ± SEM (error bars). *, **, **, p<0.05, 0.01, 0.001 respectively compared with control (One-way ANOVA with Dunnett's post-test).
Mentions: Treatment with TLR agonists; Pam3CSK (TLR 1/2 agonist), POLY (I:C) (TLR 3 agonist), Rec FLA-ST (TLR 5 agonist) and FSL-1 (TLR 2/6 agonist), had no effect on CAMP expression in END E6/E7 and ECT E6/E7 cells compared to untreated controls, but markedly up-regulated expression of DEFB4 (Figure 3). In contrast, treatment with 25(OH) vitamin D3 and 1, 25(OH) vitamin D3 up-regulated the expression of CAMP, but not DEFB4 in END E6/E7 and ECT E6/E7 cell lines (Figure 4). Treatment with 25(OH) vitamin D3 also increased the expression of the gene encoding 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) which catalyses the conversion of 25(OH) vitamin D3 to 1, 25(OH) vitamin D3 in each cell line (Figure 5).

Bottom Line: The aim of this study was to investigate cathelicidin production, regulation and function in the cervix. hCAP18/LL-37 was found to be present in cervicovaginal secretions collected from women in the first trimester of pregnancy and to be expressed at significantly higher levels in samples from women with alterations in vaginal bacterial flora characteristic of bacterial vaginosis.However, no association was found between serum levels of vitamin D and hCAP18/LL-37 concentrations in cervicovaginal secretions (n = 116).Further investigation will elucidate the effects of hCAP18/LL-37 on the physiology and pathophysiology of labour, and may lead to strategies for the prevention of infection-associated preterm birth.

View Article: PubMed Central - PubMed

Affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
hCAP18/LL-37 is the sole human cathelicidin; a family of host defence peptides with key roles in innate host defence. hCAP18/LL-37 is expressed primarily by neutrophils and epithelial cells, but its production and function in the lower genital tract is largely uncharacterised. Despite the significant roles for cathelicidin in multiple organs and inflammatory processes, its impact on infections that could compromise fertility and pregnancy is unknown. The aim of this study was to investigate cathelicidin production, regulation and function in the cervix. hCAP18/LL-37 was found to be present in cervicovaginal secretions collected from women in the first trimester of pregnancy and to be expressed at significantly higher levels in samples from women with alterations in vaginal bacterial flora characteristic of bacterial vaginosis. In endocervical epithelial cell lines, expression of the gene encoding hCAP18/LL-37 (CAMP) was not affected by TLR agonists, but was found to be up-regulated by both 1, 25 hydroxyvitamin D3 and 25 hydroxyvitamin D3. However, no association was found between serum levels of vitamin D and hCAP18/LL-37 concentrations in cervicovaginal secretions (n = 116). Exposure to synthetic LL-37 had a pro-inflammatory effect on endocervical epithelial cell lines, increasing secretion of inflammatory cytokine IL-8. Together these data demonstrate inducible expression of hCAP18/LL-37 in the female lower reproductive tract in vivo and suggest the capacity for this peptide to modulate host defence to infection in this system. Further investigation will elucidate the effects of hCAP18/LL-37 on the physiology and pathophysiology of labour, and may lead to strategies for the prevention of infection-associated preterm birth.

Show MeSH
Related in: MedlinePlus