Soluble transition metals in welding fumes cause inflammation via activation of NF-B and AP-1

J.D. McNeilly, L. A. Jimenez, M. F. Clay, W MacNee, A. Howe, M.R. Heal, I J Beverland, K. Donaldson

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We previously reported that the molecular pro-inflammatory effects of welding fumes in vitro were caused by soluble transition metals via an oxidative stress-mediated mechanism. Herein, we tested the hypothesis that transition metals in welding fume drive the in vivo inflammatory response caused by welding fume. Rats were instilled with either whole, soluble extract or washed welding fume particulates or soluble extracts pre-treated with a transition metal chelator. Markers of pulmonary inflammation were measured in the bronchoalveolar lavage fluid (BALF) and nuclear translocation of transcription factor was assessed in BAL cells by electrophoretic mobility shift assay. Instillation of either whole or soluble fractions of welding fume caused a significant influx of inflammatory cells and other markers of inflammation in the BALF 24 h later. MIP-2 protein in BALF and nuclear translocation of NF-kappaB and AP-1 were significantly greater following instillation of whole and soluble fractions than in saline-instilled lungs. Chelation of the soluble fraction, to remove transition metals, abolished the ability to cause inflammation, MIP-2 increase or transcription factor translocation to the nucleus. Instillation of washed particulates alone caused no significant change in any end-point compared to saline. This study demonstrates that soluble transition metals present in welding fumes cause inflammation via activation of the redox-sensitive transcription factors NF-kappaB and AP-1 and confirms the validity of utilising in vitro models to assess inflammatory responses to such particles.

LanguageEnglish
Pages152-157
JournalToxicology Letters
Volume158
Issue number2
DOIs
Publication statusPublished - 2004

Fingerprint

Welding
Fumes
Transcription Factor AP-1
Transition metals
Metals
Chemical activation
Inflammation
Bronchoalveolar Lavage Fluid
Transcription Factors
NF-kappa B
Fluids
Dimercaprol
Electrophoretic mobility
Oxidative stress
Electrophoretic Mobility Shift Assay
Chelating Agents
Chelation
Oxidation-Reduction
Rats
Assays

Keywords

  • molecular pro-inflammatory effects
  • welding fumes
  • soluble transition metals
  • oxidative stress-mediated mechanism
  • in vivo inflammatory response
  • pulmonary inflammation
  • bronchoalveolar lavage fluid (BALF)
  • MIP-2 protein

Cite this

McNeilly, J. D., Jimenez, L. A., Clay, M. F., MacNee, W., Howe, A., Heal, M. R., ... Donaldson, K. (2004). Soluble transition metals in welding fumes cause inflammation via activation of NF-B and AP-1. Toxicology Letters, 158(2), 152-157. https://doi.org/10.1016/j.toxlet.2005.03.005
McNeilly, J.D. ; Jimenez, L. A. ; Clay, M. F. ; MacNee, W ; Howe, A. ; Heal, M.R. ; Beverland, I J ; Donaldson, K. / Soluble transition metals in welding fumes cause inflammation via activation of NF-B and AP-1. In: Toxicology Letters. 2004 ; Vol. 158, No. 2. pp. 152-157.
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McNeilly, JD, Jimenez, LA, Clay, MF, MacNee, W, Howe, A, Heal, MR, Beverland, IJ & Donaldson, K 2004, 'Soluble transition metals in welding fumes cause inflammation via activation of NF-B and AP-1' Toxicology Letters, vol. 158, no. 2, pp. 152-157. https://doi.org/10.1016/j.toxlet.2005.03.005

Soluble transition metals in welding fumes cause inflammation via activation of NF-B and AP-1. / McNeilly, J.D.; Jimenez, L. A.; Clay, M. F.; MacNee, W; Howe, A.; Heal, M.R.; Beverland, I J; Donaldson, K.

In: Toxicology Letters, Vol. 158, No. 2, 2004, p. 152-157.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Soluble transition metals in welding fumes cause inflammation via activation of NF-B and AP-1

AU - McNeilly, J.D.

AU - Jimenez, L. A.

AU - Clay, M. F.

AU - MacNee, W

AU - Howe, A.

AU - Heal, M.R.

AU - Beverland, I J

AU - Donaldson, K.

PY - 2004

Y1 - 2004

N2 - We previously reported that the molecular pro-inflammatory effects of welding fumes in vitro were caused by soluble transition metals via an oxidative stress-mediated mechanism. Herein, we tested the hypothesis that transition metals in welding fume drive the in vivo inflammatory response caused by welding fume. Rats were instilled with either whole, soluble extract or washed welding fume particulates or soluble extracts pre-treated with a transition metal chelator. Markers of pulmonary inflammation were measured in the bronchoalveolar lavage fluid (BALF) and nuclear translocation of transcription factor was assessed in BAL cells by electrophoretic mobility shift assay. Instillation of either whole or soluble fractions of welding fume caused a significant influx of inflammatory cells and other markers of inflammation in the BALF 24 h later. MIP-2 protein in BALF and nuclear translocation of NF-kappaB and AP-1 were significantly greater following instillation of whole and soluble fractions than in saline-instilled lungs. Chelation of the soluble fraction, to remove transition metals, abolished the ability to cause inflammation, MIP-2 increase or transcription factor translocation to the nucleus. Instillation of washed particulates alone caused no significant change in any end-point compared to saline. This study demonstrates that soluble transition metals present in welding fumes cause inflammation via activation of the redox-sensitive transcription factors NF-kappaB and AP-1 and confirms the validity of utilising in vitro models to assess inflammatory responses to such particles.

AB - We previously reported that the molecular pro-inflammatory effects of welding fumes in vitro were caused by soluble transition metals via an oxidative stress-mediated mechanism. Herein, we tested the hypothesis that transition metals in welding fume drive the in vivo inflammatory response caused by welding fume. Rats were instilled with either whole, soluble extract or washed welding fume particulates or soluble extracts pre-treated with a transition metal chelator. Markers of pulmonary inflammation were measured in the bronchoalveolar lavage fluid (BALF) and nuclear translocation of transcription factor was assessed in BAL cells by electrophoretic mobility shift assay. Instillation of either whole or soluble fractions of welding fume caused a significant influx of inflammatory cells and other markers of inflammation in the BALF 24 h later. MIP-2 protein in BALF and nuclear translocation of NF-kappaB and AP-1 were significantly greater following instillation of whole and soluble fractions than in saline-instilled lungs. Chelation of the soluble fraction, to remove transition metals, abolished the ability to cause inflammation, MIP-2 increase or transcription factor translocation to the nucleus. Instillation of washed particulates alone caused no significant change in any end-point compared to saline. This study demonstrates that soluble transition metals present in welding fumes cause inflammation via activation of the redox-sensitive transcription factors NF-kappaB and AP-1 and confirms the validity of utilising in vitro models to assess inflammatory responses to such particles.

KW - molecular pro-inflammatory effects

KW - welding fumes

KW - soluble transition metals

KW - oxidative stress-mediated mechanism

KW - in vivo inflammatory response

KW - pulmonary inflammation

KW - bronchoalveolar lavage fluid (BALF)

KW - MIP-2 protein

U2 - 10.1016/j.toxlet.2005.03.005

DO - 10.1016/j.toxlet.2005.03.005

M3 - Article

VL - 158

SP - 152

EP - 157

JO - Toxicology Letters

T2 - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

IS - 2

ER -