title: Innate immunity in the vagina (part I): estradiol inhibits HBD2 and elafin secretion by human vaginal epithelial cells.
abstract: OBJECTIVE
  Vaginal epithelial cells (VEC) are the first line of defense against incoming pathogens in the female reproductive tract. Their ability to produce the anti-HIV molecules elafin and HBD2 under hormonal stimulation is unknown.
  
  
  METHODS
  Vaginal epithelial cells were recovered using a menstrual cup and cultured overnight prior to treatment with estradiol (E₂), progesterone (P₄) or a panel of selective estrogen response modulators (SERMs). Conditioned media were recovered and analyzed for protein concentration and anti-HIV activity.
  
  
  RESULTS
  E₂ significantly decreased the secretion of HBD2 and elafin by VEC over 48 hrs, while P4 and the SERMs (tamoxifen, PHTTP, ICI or Y134) had no effect. VEC conditioned media from E₂ -treated cells had no anti-HIV activity, while that from E₂ /P₄ -treated cells significantly inhibited HIV-BaL infection.
  
  
  CONCLUSIONS
  The menstrual cup allows for effective recovery of primary VEC. Their production of HBD2 and elafin is sensitive to E₂, suggesting that innate immune protection varies in the vagina across the menstrual cycle.
authors: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. Mickey.V.Patel@Dartmouth.edu
authors: Mickey V
authors: MV
authors: Patel
authors: John V
authors: JV
authors: Fahey
authors: Richard M
authors: RM
authors: Rossoll
authors: Charles R
authors: CR
authors: Wira
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000032:analysis; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D053492:Elafin / Q000032:analysis / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008875:Middle Aged; D011374:Progesterone / Q000494:pharmacology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D014621:Vagina / Q000166:cytology / Q000276:immunology*; D023083:beta-Defensins / Q000032:analysis / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D017077:Culture Media, Conditioned; C106641:DEFB4A protein, human; D053492:Elafin; D020845:Selective Estrogen Receptor Modulators; D023083:beta-Defensins; D011374:Progesterone; D004958:Estradiol
references: Biol Reprod. 2000 Apr;62(4):821-30
references: 10727249
references: Innate Immun. 2013;19(2):121-31
references: 22855555
references: Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905
references: 12019106
references: Curr Opin HIV AIDS. 2012 Mar;7(2):172-9
references: 22274658
references: Biol Reprod. 1999 Feb;60(2):508-14
references: 9916021
references: Biol Cell. 1991;73(1):49-56
references: 1726420
references: J Reprod Immunol. 2011 Dec;92(1-2):88-96
references: 21940052
references: Am J Reprod Immunol. 2009 Jul;62(1):60-71
references: 19527233
references: AIDS. 2008 Oct 1;22(15):1909-17
references: 18784454
references: Reproduction. 2008 Jun;135(6):739-49
references: 18502890
references: Tissue Cell. 2008 Apr;40(2):95-102
references: 18031781
references: J Clin Invest. 1996 Sep 15;98(6):1389-99
references: 8823304
references: PLoS One. 2010 Dec 14;5(12):e14306
references: 21179465
references: Curr Probl Dermatol. 2011;40:9-19
references: 21325836
references: Am J Reprod Immunol. 2013 Feb;69(2):159-67
references: 23025258
references: J Virol. 2005 Nov;79(22):14318-29
references: 16254366
references: Contraception. 1999 Feb;59(2):91-5
references: 10361623
references: Mucosal Immunol. 2011 May;4(3):335-42
references: 21048705
references: Infect Immun. 2005 Jul;73(7):4231-7
references: 15972514
references: Biol Reprod. 2005 Apr;72(4):814-21
references: 15576826
references: Am J Reprod Immunol. 2012 Jan;67(1):44-53
references: 21883619
references: BMC Vet Res. 2012 Mar 19;8:31
references: 22429795
references: J Leukoc Biol. 2005 Jul;78(1):158-66
references: 15831560
references: Adv Dent Res. 2006 Apr 01;19(1):42-8
references: 16672548
references: Infect Immun. 1988 Oct;56(10):2558-62
references: 3262088
references: J Infect Dis. 2005 Nov 15;192(10):1731-40
references: 16235171
references: Cytokine. 2010 Feb;49(2):209-14
references: 19819163
references: Microbes Infect. 2005 Jul;7(9-10):1117-27
references: 15893496
references: Hum Reprod. 2006 May;21(5):1135-42
references: 16531471
references: J Infect Dis. 2011 Aug 1;204(3):391-9
references: 21730203
references: J Infect Dis. 2001 Dec 1;184(11):1489-93
references: 11709796
references: Immunology. 2010 Feb;129(2):207-19
references: 19824918
references: J Leukoc Biol. 2010 Sep;88(3):435-44
references: 20385795
references: Infect Immun. 2002 Feb;70(2):577-83
references: 11796585
references: Mucosal Immunol. 2008 Jul;1(4):317-25
references: 19079193
references: J Pharmacol Exp Ther. 2000 Nov;295(2):431-7
references: 11046073
references: Fertil Steril. 1997 Sep;68(3):560-4
references: 9314936
references: Mol Hum Reprod. 1999 Jul;5(7):656-61
references: 10381821
references: AIDS. 2003 Nov 7;17(16):F39-48
references: 14571200
references: Am J Reprod Immunol. 2011 Mar;65(3):334-43
references: 21223421
references: PLoS One. 2010 Jun 29;5(6):e11366
references: 20614007
references: J Biomed Sci. 2012 Jun 20;19:58
references: 22715972
references: J Reprod Immunol. 2011 Mar;88(2):185-94
references: 21353708
references: Am J Obstet Gynecol. 2000 Oct;183(4):967-73
references: 11035348
references: Nat Rev Immunol. 2006 Jun;6(6):447-56
references: 16724099
references: AIDS. 2009 Aug 24;23(13):1669-77
references: 19553806
references: Arch Histol Cytol. 2004 Dec;67(5):417-34
references: 15781983