Abstract

Background: Organic dust exposure results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory diseases. Mechanisms underlying this modulated response are not clear. Objective: This study investigated the effects of repeat versus single organic dust exposure-induced inflammatory mediators and protein kinase C (PKC) activity in monocytes. Methods: Settled organic dust was obtained from swine confinement facilities. Promonocytic THP-1 cells and human peripheral blood monocytes were pretreated with or without dust extract and then restimulated. Culture supernatants were evaluated for TNF-α, IL-6, CXCL8, and IL-10. Responses were compared with endotoxin-depleted dust, LPS, and peptidoglycan. PKC isoform (α, δ, ε, ζ) activation was evaluated by direct kinase activity. PKC isoform inhibitors' effects on TNF-α secretion were studied. Results: Single exposure to organic dust stimulated monocyte secretion of TNF-α, IL-6, CXCL8, and IL-10 compared with unstimulated cells. TNF-α and IL-6 were diminished in pretreated cells restimulated with dust. Secretion of CXCL8 and IL-10 remained persistently elevated. TNF-α responses were retained after marked depletion of endotoxin. Dust exposure induced significant PKC α, δ, ε, and ζ activation, peaking at 30 to 60 minutes. PKC isoform activation was attenuated in repeat exposed cells. Inhibition of PKCα and PKCε reduced dust-induced TNF-α secretion. Conclusion: Repeat organic dust exposure modulated inflammatory mediator production in monocytes independent of endotoxin. The inability of PKC to be reactivated may account for this observation. Clinical implications: Targeting PKC and specific mediators associated with repetitive organic dust exposure may result in novel therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)366-373
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number2
DOIs
StatePublished - Aug 2007

Keywords

  • Monocyte
  • adaptation
  • cytokines
  • inflammation
  • organic dust
  • protein kinase C
  • swine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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