title: Human cathelicidin production by the cervix.
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.
authors.affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Frew
authors.affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Sofia
authors.initials: S
authors.lastname: Makieva
authors.affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Andrew T M
authors.initials: AT
authors.lastname: McKinlay
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McHugh
authors.affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ann
authors.initials: A
authors.lastname: Doust
authors.affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.affiliation: Tommy's centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Stock
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002112:Calcifediol / Q000494:pharmacology; D002460:Cell Line; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism*; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D011247:Pregnancy; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D016585:Vaginosis, Bacterial / Q000378:metabolism; D014807:Vitamin D / Q000097:blood / Q000494:pharmacology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D016209:Interleukin-8; D051193:Toll-Like Receptors; D014807:Vitamin D; D002112:Calcifediol; D054804:Cathelicidins
references.citation: J Inflamm (Lond). 2013 Apr 11;10(1):15
references.pmid: 23577829
references.citation: PLoS One. 2010 Dec 14;5(12):e15580
references.pmid: 21179490
references.citation: J Immunol. 2009 Apr 1;182(7):4289-95
references.pmid: 19299728
references.citation: Infect Immun. 2005 Jan;73(1):583-91
references.pmid: 15618198
references.citation: J Biol Chem. 2008 Nov 7;283(45):30471-81
references.pmid: 18765670
references.citation: J Allergy Clin Immunol. 2011 May;127(5):1302-4.e1
references.pmid: 21310475
references.citation: J Immunol. 2013 Jul 15;191(2):934-41
references.pmid: 23752614
references.citation: J Immunol. 2006 Mar 1;176(5):3044-52
references.pmid: 16493063
references.citation: J Invest Dermatol. 2008 Jan;128(1):223-36
references.pmid: 17805349
references.citation: Int J Dermatol. 2009 Aug;48(8):846-54
references.pmid: 19659863
references.citation: J Immunol. 2009 Aug 15;183(4):2688-96
references.pmid: 19605696
references.citation: J Hum Nutr Diet. 2014 Jun;27(3):261-9
references.pmid: 24033613
references.citation: J Immunol. 2013 Feb 1;190(3):1217-26
references.pmid: 23267025
references.citation: PLoS One. 2012;7(2):e31996
references.pmid: 22389677
references.citation: Infect Immun. 2006 Oct;74(10):5693-702
references.pmid: 16988245
references.citation: FEMS Immunol Med Microbiol. 2006 Oct;48(1):75-83
references.pmid: 16965354
references.citation: AIDS. 2009 Jan 28;23(3):309-17
references.pmid: 19114868
references.citation: Am J Physiol Cell Physiol. 2011 Jan;300(1):C105-12
references.pmid: 20943960
references.citation: Am J Perinatol. 2011 Jan;28(1):7-12
references.pmid: 20640974
references.citation: Br J Nutr. 2013 Mar 14;109(5):898-905
references.pmid: 23168244
references.citation: BMC Res Notes. 2012 Oct 24;5:575
references.pmid: 23095332
references.citation: J Clin Microbiol. 1991 Feb;29(2):297-301
references.pmid: 1706728
references.citation: Reprod Sci. 2009 Dec;16(12):1125-34
references.pmid: 19723838
references.citation: Am J Respir Crit Care Med. 2002 Apr 1;165(7):992-5
references.pmid: 11934727
references.citation: Matern Child Nutr. 2013 Jan;9(1):23-30
references.pmid: 23230904
references.citation: J Immunol. 2008 Nov 15;181(10):7115-20
references.pmid: 18981132
references.citation: PLoS One. 2009 Jun 05;4(6):e5810
references.pmid: 19503839
references.citation: J Leukoc Biol. 2004 Jan;75(1):39-48
references.pmid: 12960280
references.citation: J Cyst Fibros. 2007 Nov 30;6(6):403-10
references.pmid: 17467345
references.citation: J Transl Med. 2009 Apr 23;7:28
references.pmid: 19389235
references.citation: Clin Infect Dis. 2009 Feb 15;48(4):418-24
references.pmid: 19133797
references.citation: Acta Paediatr. 2010 Jun;99(6):836-41
references.pmid: 20178514
references.citation: J Immunol. 2004 Jan 15;172(2):1146-56
references.pmid: 14707090
references.citation: Ann Surg. 2002 Jan;235(1):113-24
references.pmid: 11753050
references.citation: Infect Immun. 1999 May;67(5):2561-6
references.pmid: 10225921
references.citation: J Immunol. 2004 Sep 1;173(5):2909-12
references.pmid: 15322146
references.citation: J Immunol. 2010 Jan 15;184(2):965-74
references.pmid: 20008294
references.citation: J Exp Med. 2000 Oct 2;192(7):1069-74
references.pmid: 11015447
references.citation: Mol Cancer Res. 2009 Jun;7(6):907-15
references.pmid: 19491199
references.citation: FASEB J. 2005 Jul;19(9):1067-77
references.pmid: 15985530
references.citation: J Clin Invest. 2003 Jun;111(11):1665-72
references.pmid: 12782669
references.citation: J Immunol. 2004 Apr 15;172(8):4987-94
references.pmid: 15067080
references.citation: FEMS Immunol Med Microbiol. 2004 Oct 1;42(2):225-31
references.pmid: 15364108
references.citation: Am J Obstet Gynecol. 2013 Feb;208(2):132.e1-7
references.pmid: 23174285
references.citation: J Leukoc Biol. 2006 Sep;80(3):509-20
references.pmid: 16793910
references.citation: Circ Res. 2013 Mar 1;112(5):792-801
references.pmid: 23283724
references.citation: Science. 2006 Mar 24;311(5768):1770-3
references.pmid: 16497887
references.citation: J Immunol. 2003 Dec 15;171(12):6690-6
references.pmid: 14662872
references.citation: J Periodontal Res. 2011 Jun;46(3):327-37
references.pmid: 21338358