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Abstract

Environmental and occupational exposure to vanadium (V) dusts results in inflammation mainly confined to the respiratory tract. Macrophages apparently play an important role in mediating the inflammation via the production of many chemokines. In the current study, we investigated whether vanadium can regulate the gene expression of a CXC chemokine macrophage inflammatory protein-2 (MIP-2), and to determine the molecular mechanisms controlling MIP-2 gene expression. A mouse macrophage cell line RAW 264.7 was treated with sodium metavanadate (NaVO3) at the dose of 0.5, 5, or 10 microg/mi V. Northern blot analysis showed that induction of MIP-2 mRNA expression was in a dose-dependent manner. To define the time course of the inflammatory response, RAW 264.7 cells were exposed to 5 microg/ml V, MIP-2 mRNA in macrophages increased markedly as early as 1 h after treatment, maximally induced at 4 h and reduced to 2-fold above control levels by 6 and 8 h. The protein levels of MIP-2 in conditioned media, measured by enzyme-linked immunosorbent assay (ELISA), was well correlated with the levels of MIP-2 mRNA following all of the treatments in the study. In addition, the increase in MIP-2 mRNA expression by vanadium was attenuated by co-treatment with the antioxidant N-acetylcysteine (NAC), at the doses of 10 and 20 mM, suggesting that the induction of MIP-2 mRNA is mediated via the generation of reactive oxygen species (ROS). To further investigate transcriptional regulation of the MIP-2 gene expression by vanadium, we performed RNA decay assay by measuring the half-life of MIP-2 mRNA. Co-treatment of macrophages with the transcriptional inhibitor actinomycin D at 5 microg/ml following exposure to 5 microg/ml V for 4 h revealed complete stabilization of vanadium-induced MIP-2 mRNA and no sign of mRNA degradation, at least, for 6 h, in comparison to the half-life of MIP-2 mRNA was approximately 2.5 h by bacterial lipopolysaccharide (LPS) treatment, supporting post-transcriptional stabilization as the predominant role of MIP-2 gene expression. In conclusion, these observations demonstrate that in vitro vanadium can induce MIP-2 mRNA expression, mediating, at least in part, via the production of ROS. In addition, the increase in MIP-2 mRNA level involves, most likely, post-transcriptional control via increased mRNA stability.

Toxicity of Vanadium Compounds: Pulmonary and Immune System Targets

“…However, it is clear that the activation of ERKs is associated with increases in inducibility of macrophage NO (that can act as a suppressor of cell activation) as well as MlP-la and MIP-2 chemoattractant formation (105,106,107). ERK activation (as seen in 56) provides one of the best plausible mechanisms to explain the in vivo and in vitro findings of Chong et al (108,109) wherein levels of both chemokines were increased by instillation of rats, or treatment of mouse RAW264.7 cells, with soluble sodium orthovanadate (NaV0 3 ).…”

Role of Macrophages in Air Pollution Exposure Related Asthma

“…The results showed that NaVO 3 could increase CXC chemokine macrophage inflammatory protein-2 (MIP-2/CXCL-2) mRNA expression in a dose-dependent manner, and the expression could be suppressed by an antioxidant N-acetylcysteine treatment. These results indicated that NaVO 3 induced CXCL-2 mRNA expression via increased oxidative stress [ 102 ]. Cohen et al studied the effect of ammonium metavanadate (NH 4 VO 3 ) and vanadium pentoxide (V 2 O 3 ) on murine macrophage-like cells.…”