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Ureaplasma spp. lipid-associated membrane proteins induce human monocyte U937 cell cycle arrest through

Xucheng Huang1, Yingli Qiao1, Yixuan Zhou1

  • 1Clinical Laboratory, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China; Biomedical Research Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.

International Journal of Medical Microbiology : IJMM
|July 24, 2018
PubMed

Insights

Lipid-associated membrane proteins (LAMPs) from Ureaplasma spp. inhibit human cell proliferation by arresting the cell cycle. These LAMPs induce G1 cell cycle arrest via p21 expression, independent of p53, offering insights into Ureaplasma pathogenesis.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Ureaplasma spp. are linked to genitourinary and perinatal diseases.
  • Lipid-associated membrane proteins (LAMPs) of Ureaplasma spp. are implicated in disease pathogenesis.
  • The precise mechanisms of Ureaplasma spp. LAMPs in disease remain largely unelucidated.

Purpose of the Study:

  • To explore the pathogenic mechanisms of Ureaplasma spp. LAMPs.
  • To investigate the role of Ureaplasma spp. LAMPs in modulating the cell cycle and signaling pathways in human monocytic U937 cells.

Main Methods:

  • Utilized ATCC reference strains (Ureaplasma parvum serovar 3 str. ATCC 27,815 and Ureaplasma urealyticum serovar 8 str. ATCC 27,618) and nine clinical isolates.
  • Assessed the effects of Ureaplasma spp. LAMPs on U937 cell proliferation and cell cycle distribution using flow cytometry.
  • Analyzed the expression levels of key cell cycle regulatory proteins (p53, p21, CDK2, CDK4, CDK6, cyclin E1) at transcriptional and translational levels.

Main Results:

  • LAMPs from U. urealyticum (UUR8) and clinical Ureaplasma spp. strains significantly inhibited U937 cell proliferation, while U. parvum (UPA3) LAMPs showed slight inhibition.
  • All tested Ureaplasma spp. LAMPs induced G1 phase cell cycle arrest in U937 cells.
  • Cell cycle arrest was linked to increased p53 and p21 levels and decreased CDK2, CDK4, CDK6, and cyclin E1. UPA3 LAMPs primarily affected cyclin E1. p53 down-regulation did not impact cell cycle distribution or p21 expression.

Conclusions:

  • LAMPs from U. urealyticum and clinical strains inhibit U937 cell proliferation by inducing G1 cell cycle arrest through p21 upregulation in a p53-independent manner.
  • U. parvum LAMPs exhibit a milder effect on cell cycle arrest.
  • Findings contribute to understanding Ureaplasma spp. pathogenesis and may inform therapeutic strategies for Ureaplasma infections.
Keywords:
Cell cycle arrestLipid-associated membrane proteins (LAMPs)U937Ureaplasma spp.p53-independent

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