title: ROS-mediated TNF-alpha and MIP-2 gene expression in alveolar macrophages exposed to pine dust.
abstract: BACKGROUND: 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. METHODS: Tumour necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) protein release, TNF-alpha 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. RESULTS: After 4 h incubation, both PD and HPD elicited a significantly (p < 0.05) increased mRNA expression of TNF-alpha and MIP-2 as well as a concentration-dependent release of TNF-alpha and MIP-2 protein. Interestingly, PD induced a significantly higher TNF-alpha 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-alpha, 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. CONCLUSION: These results indicate that pine dust is able to induce expression of TNF-alpha and MIP-2 in rat alveolar macrophages by a mechanism that is, at least in part, mediated by ROS.
authors.affiliation: Institute for Surgical Research, University of Munich, Munich, Germany. krombach@med.uni-muenchen.de.
authors.forename: Huayan
authors.initials: H
authors.lastname: Long
authors.forename: Tingming
authors.initials: T
authors.lastname: Shi
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Borm
authors.forename: Juha
authors.initials: J
authors.lastname: Määttä
authors.forename: Kirsti
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
authors.forename: Kai
authors.initials: K
authors.lastname: Savolainen
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach