Zariffard M Reza, Anastos Kathryn, French Audrey L, Munyazesa Elisaphane, Cohen Mardge, Landay Alan L, Spear Gregory T
Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
Departments of Medicine and Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, United States of America.
PLoS One. 2015 Jan 22;10(1):e0116911. doi: 10.1371/journal.pone.0116911. eCollection 2015.
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.
Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA.
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.
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.
白细胞介素-8（IL-8，CXCL8）在包括下生殖道在内的黏膜部位的免疫反应中发挥重要作用。由于几种细菌会产生可切割IL-8的蛋白酶，且下生殖道微生物群中可能存在多种细菌，我们评估了生殖道分泌物中IL-8的切割/改变情况。
通过灌洗收集了200名女性（23名HIV血清阴性和177名HIV血清阳性）的生殖道分泌物，采用酶联免疫吸附测定法检测IL-8的切割/改变情况。
在HIV阳性女性（28%）和HIV阴性女性（35%）的分泌物中均观察到IL-8切割/改变活性。通过16S rRNA基因高通量测序确定，该活性与下生殖道中存在的细菌类型之间没有明确关系。基质金属蛋白酶（MMP）特异性蛋白酶抑制剂可降低该活性，一项检测无活性和活性MMP的多重检测显示，许多女性的生殖道分泌物中存在多种MMP，包括MMP-1、-3、-7、-8、-9、-10和-12。IL-8切割/改变活性与活性MMP-9以及几种活性MMP作用的底物的切割显著相关。
这些研究表明，女性生殖道中存在多种MMP，强烈提示生殖道分泌物中的MMP-9可在该黏膜部位切割IL-8。这些研究表明，MMP介导的IL-8切割可调节下生殖道的炎症反应。
