ROS-mediated TNF-α and MIP-2 gene expression in alveolar macrophages exposed to pine dust

• Main Authors: Husgafvel-Pursiainen Kirsti, Määttä Juha, Borm Paul J, Shi Tingming, Long Huayan, Savolainen Kai, Krombach Fritz
• Format: Article
• Language: English
• Published: BMC 2004-12-01
• Series: Particle and Fibre Toxicology
• Online Access: http://www.particleandfibretoxicology.com/content/1/1/3

<p>Abstract</p> <p>Background</p> <p>Respiratory symptoms, impaired lung function, and asthma have been reported in workers exposed to wood dust in a number of epidemiological studies. The underlying pathomechanisms, however, are not well understood. Here, we studied the effects of dust from pine (PD) and heat-treated pine (HPD) on the release of reactive oxygen species (ROS) and inflammatory mediators in rat alveolar macrophages.</p> <p>Methods</p> <p>Tumour necrosis factor-alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2) protein release, TNF-α and MIP-2 mRNA expression, and generation of ROS were studied as end points after treatment of rat alveolar macrophages with PD or HPD. In a separate series of experiments, the antioxidants glutathione and N-acetyl-L-cysteine were included in combination with wood dust. To determine the endogenous oxidative and antioxidant capacity of wood dusts, electron spin resonance (ESR) spectroscopy was used.</p> <p>Results</p> <p>After 4 h incubation, both PD and HPD elicited a significantly (p < 0.05) increased mRNA expression of TNF-α and MIP-2 as well as a concentration-dependent release of TNF-α and MIP-2 protein. Interestingly, PD induced a significantly higher TNF-α and MIP-2 production than HPD. Moreover, a significantly increased ROS production was observed in alveolar macrophages exposed to both PD and HPD. In the presence of the antioxidants glutathione and N-acetyl-L-cysteine, the PD- and HPD-induced release of ROS, TNF-α, and MIP-2 was significantly reduced. Finally, electron spin resonance analyses demonstrated a higher endogenous antioxidant capacity of HPD compared to PD. Endotoxin was not present in either dust sample.</p> <p>Conclusion</p> <p>These results indicate that pine dust is able to induce expression of TNF-α and MIP-2 in rat alveolar macrophages by a mechanism that is, at least in part, mediated by ROS.</p>