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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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Cervical hCAP18/LL-37 expression.(A) Correlation between cervicovaginal hCAP18/LL-37 and Myeloperoxidase (r = 0.1; n = 77; p = 0.3). (B) Representative western blot of hCAP18/LL-37 expression in cervicovaginal secretions. The 18 kDa hCAP18 and the 5–10 kDa cleaved peptide LL-37 were detected in cervicovaginal secretions.
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pone-0103434-g001: Cervical hCAP18/LL-37 expression.(A) Correlation between cervicovaginal hCAP18/LL-37 and Myeloperoxidase (r = 0.1; n = 77; p = 0.3). (B) Representative western blot of hCAP18/LL-37 expression in cervicovaginal secretions. The 18 kDa hCAP18 and the 5–10 kDa cleaved peptide LL-37 were detected in cervicovaginal secretions.

Mentions: hCAP18/LL-37 was detected in 79/130 (60.8%) samples of cervicovaginal secretions with a median concentration of 0.3 ng/mg total protein (range 0.14–0.68 ng/mg total protein). To investigate whether neutrophils were the main source of hCAP18/LL-37 we examined the correlation between myeloperoxidase (MPO), a neutrophil granule product, and hCAP18/LL-37. A weak positive correlation was found between cervicovaginal MPO and cervicovaginal hCAP18/LL-37 (r = 0.1; n = 77, p = 0.3), the limited strength suggesting that neutrophils were not the predominant source of hCAP18/LL-37 (Figure 1A).


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)

Cervical hCAP18/LL-37 expression.(A) Correlation between cervicovaginal hCAP18/LL-37 and Myeloperoxidase (r = 0.1; n = 77; p = 0.3). (B) Representative western blot of hCAP18/LL-37 expression in cervicovaginal secretions. The 18 kDa hCAP18 and the 5–10 kDa cleaved peptide LL-37 were detected in cervicovaginal secretions.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0103434-g001: Cervical hCAP18/LL-37 expression.(A) Correlation between cervicovaginal hCAP18/LL-37 and Myeloperoxidase (r = 0.1; n = 77; p = 0.3). (B) Representative western blot of hCAP18/LL-37 expression in cervicovaginal secretions. The 18 kDa hCAP18 and the 5–10 kDa cleaved peptide LL-37 were detected in cervicovaginal secretions.
Mentions: hCAP18/LL-37 was detected in 79/130 (60.8%) samples of cervicovaginal secretions with a median concentration of 0.3 ng/mg total protein (range 0.14–0.68 ng/mg total protein). To investigate whether neutrophils were the main source of hCAP18/LL-37 we examined the correlation between myeloperoxidase (MPO), a neutrophil granule product, and hCAP18/LL-37. A weak positive correlation was found between cervicovaginal MPO and cervicovaginal hCAP18/LL-37 (r = 0.1; n = 77, p = 0.3), the limited strength suggesting that neutrophils were not the predominant source of hCAP18/LL-37 (Figure 1A).

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