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 Harold Limper

Research output: Contribution to journalArticle

82 Citations (Scopus)

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 2005

Fingerprint

Pneumocystis
Alveolar Epithelial Cells
Glucans
Chemokines
Cell Wall
Cells
Chemokine CXCL2
Pneumocystis carinii
Pneumocystis Pneumonia
Cytokines
Protein Kinase C
Tumor Necrosis Factor-alpha
Cellular Structures
Respiratory Insufficiency
Epithelial Cells
Rats
Pneumonia
Transcription Factors
Chemical activation
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Pneumocystis cell wall β-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-κB-dependent mechanisms. / Evans, Scott E.; Hahn, Peter Y.; McCann, Frances; Kottom, Theodore J.; Pavlović, Zvezdana Vuk; Limper, Andrew Harold.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 32, No. 6, 06.2005, p. 490-497.

Research output: Contribution to journalArticle

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