Pneumocystis carinii inhibits cyclin-dependent kinase activity in lung epithelial cells

Andrew H. Limper, Maryanne Edens, Robert A. Anders, Edward B. Leof

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Pneumocystis carinii remains an important cause of pneumonia in patients with AIDS. Attachment of the organism to epithelial cells is a central event in establishing infection, impairing the growth potential of lung epithelial cells and thereby slowing repair. In light of investigations documenting a central role for cyclin-dependent kinases in controlling the cell cycle, we addressed the hypothesis that P. carinii inhibits epithelial cell growth by interfering with host epithelial cyclin-dependent kinase (cdk) activity. We observed that P. carinii significantly impaired growth of cultured mink lung epithelial cells, with effects observed after 48-72 h of treatment. However, the kinase activity associated with p34(cdc2) or p33(cdk2) was maximally inhibited as early as 24 h after P. carinii exposure. The inhibitory effect on cyclin-dependent kinase activity was mediated by the trophozoite form of P. carinii, in that highly purified trophozoites exerted marked inhibition of p34(cdc2) activity. Growth impairment was similarly preceded by P. carinii- induced alteration in the state of epithelial cell p34(cdc2) phosphorylation, with no change in p34(cdc2) or p33(cdk2) protein levels. These data strongly suggest that the antiproliferative activity of P. carinii on respiratory epithelium is mediated in part through modulation of the host cell cycle machinery.

Original languageEnglish (US)
Pages (from-to)1148-1155
Number of pages8
JournalJournal of Clinical Investigation
Volume101
Issue number5
DOIs
StatePublished - Mar 1 1998

Keywords

  • Cell cycle
  • Cyclin-dependent kinase
  • Epithelium
  • Pneumocystis carinii

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Pneumocystis carinii inhibits cyclin-dependent kinase activity in lung epithelial cells'. Together they form a unique fingerprint.

  • Cite this