Critical role of glass fiber length in TNF-alpha production and transcription factor activation in macrophages

Citation
Jp. Ye et al., Critical role of glass fiber length in TNF-alpha production and transcription factor activation in macrophages, AM J P-LUNG, 20(3), 1999, pp. L426-L434
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN journal
1040-0605 → ACNP
Volume
20
Issue
3
Year of publication
1999
Pages
L426 - L434
Database
ISI
SICI code
1040-0605(199903)20:3<L426:CROGFL>2.0.ZU;2-1
Abstract
Recent studies have demonstrated that dielectrophoresis is an efficient met hod for the separation of fibers according to fiber length. This method all ows the investigation of fiber-cell interactions with fiber samples of the same composition but of different lengths. In the present study, we analyze d the effects of length on the interaction between glass fibers and macroph ages by focusing on production of the inflammatory cytokine tumor necrosis factor (TNF)-alpha in a mouse macrophage cell line (RAW 264.7). The underly ing molecular mechanisms controlling TNF-alpha production were investigated at the gene transcription level. The results show that glass fibers induce d TNF-alpha production in macrophages and that this induction was associate d with activation of the gene promoter. Activation of the transcription fac tor nuclear factor (NF)-kappa B was responsible for this induced promoter a ctivity. The inhibition of both TNF-alpha production and NF-kappa B activat ion by N-acetyl-L-cysteine, an antioxidant. indicates that generation of ox idants mag contribute to the induction of this cytokine and activation of t his transcription factor by glass fibers. Long fibers (17 mu m) were signif icantly more potent than short fibers (7 mu m) in inducing NF-kappa B activ ation, the gene promoter activity, and the production of TNF-alpha. This fi ber length-dependent difference in the stimulatory potency correlated with the fact that macrophages were able to completely engulf short glass fibers , whereas phagocytosis of long glass fibers was incomplete. These results s uggest that fiber length plays a critical role in the potential pathogenici ty of glass fibers.