Ureaplasma isolates stimulate pro-inflammatory CC chemokines and matrix metalloproteinase-9 in neonatal and adult monocytes

PLoS One. 2018 Mar 20;13(3):e0194514. doi: 10.1371/journal.pone.0194514. eCollection 2018.

Abstract

Being generally regarded as commensal bacteria, the pro-inflammatory capacity of Ureaplasma species has long been debated. Recently, we confirmed Ureaplasma-driven pro-inflammatory cytokine responses and a disturbance of cytokine equilibrium in primary human monocytes in vitro. The present study addressed the expression of CC chemokines and matrix metalloproteinase-9 (MMP-9) in purified term neonatal and adult monocytes stimulated with serovar 8 of Ureaplasma urealyticum (Uu) and serovar 3 of U. parvum (Up). Using qRT-PCR and multi-analyte immunoassay, we assessed mRNA and protein expression of the monocyte chemotactic proteins 1 and 3 (MCP-1/3), the macrophage inflammatory proteins 1α and 1β (MIP-1α/β) as well as MMP-9. For the most part, both isolates stimulated mRNA expression of all given chemokines and MMP-9 in cord blood and adult monocytes (p<0.05 and p<0.01). These results were paralleled by Uu and Up-induced secretion of MCP-1 protein in both cells (neonatal: p<0.01, adult: p<0.05 and p<0.01). Release of MCP-3, MIP-1α, MIP-1β and MMP-9 was enhanced upon exposure to Up (neonatal: p<0.05, p<0.01 and p<0.001, respectively; adult: p<0.05). Co-stimulation of LPS-primed monocytes with Up increased LPS-induced MCP-1 release in neonatal cells (p<0.05) and aggravated LPS-induced MMP-9 mRNA in both cell subsets (neonatal: p<0.05, adult: p<0.01). Our results document considerable expression of pro-inflammatory CC chemokines and MMP-9 in human monocytes in response to Ureaplasma isolates in vitro, adding to our previous data. Findings from co-stimulated cells indicate that Ureaplasma may modulate monocyte immune responses to a second stimulus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Chemokines, CC / immunology
  • Chemokines, CC / metabolism*
  • Escherichia coli / immunology
  • Fetal Blood / cytology
  • Fetal Blood / metabolism
  • Humans
  • Immunity, Cellular
  • Infant, Newborn
  • Lipopolysaccharides / immunology
  • Matrix Metalloproteinase 9 / immunology
  • Matrix Metalloproteinase 9 / metabolism*
  • Monocytes / immunology*
  • Monocytes / metabolism
  • RNA, Messenger / metabolism
  • Ureaplasma urealyticum / immunology*
  • Ureaplasma urealyticum / isolation & purification
  • Urinary Tract Infections / immunology*
  • Urinary Tract Infections / microbiology

Substances

  • Chemokines, CC
  • Lipopolysaccharides
  • RNA, Messenger
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This project was supported by the Interdisciplinary Center for Clinical Research (IZKF) at the University of Würzburg, Germany. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.