Pneumocystis cell wall β-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-κB-dependent mechanisms

Scott E. Evans, Peter Y. Hahn, Frances McCann, Theodore J. Kottom, Zvezdana Vuk Pavlović, Andrew H. Limper

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Exuberant inflammatory responses are associated with respiratory failure during Pneumocystis pneumonia. Alveolar epithelial cells (AECs) promote Pneumocystis attachment and proliferation, but also contribute prominently to host cytokine-mediated inflammation during pneumonia. Recent investigations indicate that AECs produce macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) following challenge with Pneumocystis carinii. Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor critical for regulation of proinflammatory cytokine expression. Herein, we assess rat AEC NF-κB responses to challenge with a P. carinii β-glucan cell wall component (PCBG). Prominent nuclear translocation of p65 NF-κB was demonstrated following PCBG challenge. NF-κB activation was in part mediated through Protein Kinase C (PKC) signaling pathways. PCBG challenge of AECs was also shown to induce MIP-2 and TNF-α mRNA production, a response that was ameliorated by NF-κB inhibition. MIP-2 protein expression was also dramatically increased by PCBG challenge, in a manner that was significantly attenuated by both PKC and NF-kappa;B inhibition. The data further demonstrate that AEC chemokine responses were not mediated by the recently described dectin-1 receptor, but instead involved participation of cell surface lactosylceramide. These data support a significant role for AECs in host responses during Pneumocystis pneumonia, and further indicate that β-glucan induces inflammatory cytokine production through NF-KB-dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)490-497
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume32
Issue number6
DOIs
StatePublished - Jun 1 2005

Keywords

  • Alveolar epithelial cells
  • Chemokines
  • Nuclear factor-κB
  • Pneumocystis

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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