title: Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female lower genital tract.
abstract: OBJECTIVE
  Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration.
  
  
  METHODS
  Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA.
  
  
  RESULTS
  IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs.
  
  
  CONCLUSIONS
  These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract.
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: M Reza
authors.initials: MR
authors.lastname: Zariffard
authors.affiliation: Departments of Medicine and Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, United States of America.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: Ruth M. Rothstein CORE Center, Stroger Hospital of Cook County, Chicago, Illinois, United States of America.
authors.forename: Audrey L
authors.initials: AL
authors.lastname: French
authors.affiliation: Rwanda Biomedical Center, National Reference Laboratory Division, Laboratory Quality Assurance Direction, Kigali, Rwanda.
authors.forename: Elisaphane
authors.initials: E
authors.lastname: Munyazesa
authors.affiliation: Ruth M. Rothstein CORE Center, Stroger Hospital of Cook County, Chicago, Illinois, United States of America.
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Spear
mesh_terms: D000328:Adult; D005260:Female; D006679:HIV Seropositivity / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D014621:Vagina / Q000378:metabolism* / Q000473:pathology
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9