Ansport mechanism of particles via the macrophage receptor with collagenous structure (MARCO). In a study of Kanno et al. an association between the uptake of fine and ultrafine particles and MARCO was shown [27]. In our study we blocked the MARCO receptor with antibodies. The reduction of CYP1B1 transcripts after ultrafine P90 treatment was not altered by blocking antibodies compared to isotype controls (data not shown). Accordingly the transport mechanism of ultrafine P90 particles appears not to be based on the MARCO receptor and the mechanism involved is still elusive. Transcription of CYP1B1 and CYP1A1 genes is regulated by the interaction between PAH and the cytosolic arylhydrocarbon receptor. Dioxin is the most potent agonist [17], but also BaP can activate the receptor complex [28]. Cigarette smoke and diesel soot contain a huge amount of PAH adsorbed to particles [29,30]. Herein we showed aPage 8 of(page number not for citation purposes)Particle and Fibre Toxicology 2009, 6:http://www.particleandfibretoxicology.com/content/6/1/BaP-mediated induction of CYP1B1 in a concentrationdependent manner (Fig. 5). Simultaneously treatment with ultrafine P90 attenuates the CYP1B1 induction. The attenuation may be less pronounced with low concentration of BaP (0.1 M) because of absorption effects of BaP onto P90 particles, which reduce the amount of bioavailable BaP. Overall these findings indicate a competing behaviour of BaP and P90. In case of low BaP concentrations (0.1 M), P90 still reduces CYP1B1 expression and this may affect its detoxifying/toxifying activity. Besides CYP-gene products, myeloperoxidase (MPO) was reported to play an important role in metabolic activation of chemical carcinogens [31]. MPO catalyzes the conversion of H2O2 into hypochlorous acid (HOCl), which is a very strong oxidant and which in turn may be responsible for the metabolic activation of inhaled chemicals or organic compounds on inhaled particles. In our investigations we screened CD14++ monocytes for expression of MPO on mRNA level after exposure to particles (Printex 90 and fine TiO2). Compared to resting monocytes (641), particle incubation (3 h) decreased MPO mRNA expression 4-fold (-2,662; not significant) (data not shown). This result indicates that particles alter the expression of a broader variety of enzymes which are involved in inflammation and the metabolism of xenobiotics. Little is known about the mechanisms and specificity of this interaction and further investigations addressing this question will be needed. Also cytokines modulate CYP-gene expression. P90induced transcription factor NF-B in PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/6833145 alveolar macrophages leads to expression of pro-inflammatory cytokines like TNF, IL-6, and IL-1 [32]. TNF in turn increases the expression of CYP1B1 [33]. Umannov?et al. report of TNF-induced increase of CYP1B1 mRNA expression and simultaneously suppression of BaP-induced CYP1A1 expression [34]. This dysregulation was found to be associated with an enhanced formation Vorinostat of DNA adducts and enhanced genotoxic effects. CYP-expression is also regulated by aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (Arnt). Wu et al. [35] discussed the reduction of AhR- and Arnt-expression as the underlying mechanism for TNF-induced decrease of CYP1A2 expression after LPS-treatment. In our system no influence of particles was detected on AhR and Arnt on transcriptional level (data not shown). While a lot is known about induction of CYP-genes little information.