Abstract
| Language | English |
|---|---|
| Pages | 152-157 |
| Journal | Toxicology Letters |
| Volume | 158 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2004 |
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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
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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 journal › Article
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 -