Dataset Information

Linking oxidative events to inflammatory and adaptive gene expression induced by exposure to an organic particulate matter component.

ABSTRACT:

Background

Toxicological studies have correlated inflammatory effects of diesel exhaust particles (DEP) with its organic constituents, such as the organic electrophile 1,2-naphthoquinone (1,2-NQ).

Objective

To elucidate the mechanisms involved in 1,2-NQ-induced inflammatory responses, we examined the role of oxidant stress in 1,2-NQ-induced expression of inflammatory and adaptive genes in a human airway epithelial cell line.

Methods

We measured cytosolic redox status and hydrogen peroxide (H2O2) in living cells using the genetically encoded green fluorescent protein (GFP)-based fluorescent indicators roGFP2 and HyPer, respectively. Expression of interleukin-8 (IL-8), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) mRNA was measured in BEAS-2B cells exposed to 1,2-NQ for 1-4 hr. Catalase overexpression and metabolic inhibitors were used to determine the role of redox changes and H2O2 in 1,2-NQ-induced gene expression.

Results

Cells expressing roGFP2 and HyPer showed a rapid loss of redox potential and an increase in H2O2 of mitochondrial origin following exposure to 1,2-NQ. Overexpression of catalase diminished the H2O2-dependent signal but not the 1,2-NQ-induced loss of reducing potential. Catalase overexpression and inhibitors of mitochondrial respiration diminished elevations in IL-8 and COX-2 induced by exposure to 1,2-NQ, but potentiated HO-1 mRNA levels in BEAS cells.

Conclusion

These data show that 1,2-NQ exposure induces mitochondrial production of H2O2 that mediates the expression of inflammatory genes, but not the concurrent loss of reducing redox potential in BEAS cells. 1,2-NQ exposure also causes marked expression of HO-1 that appears to be enhanced by suppression of H2O2. These findings shed light into the oxidant-dependent events that underlie cellular responses to environmental electrophiles.

SUBMITTER: Cheng WY

PROVIDER: S-EPMC3279454 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Publications

Linking oxidative events to inflammatory and adaptive gene expression induced by exposure to an organic particulate matter component.

Cheng Wan-Yun WY Currier Jenna J Bromberg Philip A PA Silbajoris Robert R Simmons Steven O SO Samet James M JM

Environmental health perspectives 20111013 2

<h4>Background</h4>Toxicological studies have correlated inflammatory effects of diesel exhaust particles (DEP) with its organic constituents, such as the organic electrophile 1,2-naphthoquinone (1,2-NQ).<h4>Objective</h4>To elucidate the mechanisms involved in 1,2-NQ-induced inflammatory responses, we examined the role of oxidant stress in 1,2-NQ-induced expression of inflammatory and adaptive genes in a human airway epithelial cell line.<h4>Methods</h4>We measured cytosolic redox status and hy ...[more]

PMID: 21997482

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Dataset Information

Linking oxidative events to inflammatory and adaptive gene expression induced by exposure to an organic particulate matter component.

Background

Objective

Methods

Results

Conclusion

Publications

Linking oxidative events to inflammatory and adaptive gene expression induced by exposure to an organic particulate matter component.

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