Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female lower genital tract

M. Reza Zariffard, Kathryn Anastos, Audrey L. French, Elisaphane Munyazesa, Mardge Cohen, Alan L. Landay, Gregory T. Spear

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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. Study Design: 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.

Original languageEnglish (US)
Article numbere0116911
JournalPloS one
Volume10
Issue number1
DOIs
StatePublished - Jan 22 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Zariffard, M. R., Anastos, K., French, A. L., Munyazesa, E., Cohen, M., Landay, A. L., & Spear, G. T. (2015). Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female lower genital tract. PloS one, 10(1), [e0116911]. https://doi.org/10.1371/journal.pone.0116911