These may change the cell composition in the lung, thereby resulting in the release of cytokines. Ma and Ma also reported that both the organic and particulate components of DEPs exhibit different biological actions, but both induce cellular oxidative stress. Together, these effects exacerbate respiratory allergy and induce DNA damage, eventually leading to the development of lung tumors. Further, the oxidative stress mediated by DEPs may be induced via various mechanisms, such as the direct generation of ROS from the surface of particles; release of soluble compounds, such as transition metals or organic compounds; altered function of mitochondria or NADPH-oxidase, and activation of inflammatory cells capable of generating ROS and reactive nitrogen species. Furthermore, the increase in the mutations induced by DEP was significantly reduced by concurrent treatment with phagocytosis inhibitors. In this study, expression of transcriptional proteins, such as p-IkBa, pSTAT3, and p65, peaked on day 14, whereas the expression of p53, phospho-p53, RANTES, and TGF-b in lung tissue peaked on day 28, after a slight timedependent increase after DEP exposure. One of the major functions of TGF-b is the inhibition of growth through the blockage of the cell cycle in the late-G1 phase and inflammatory resolution by immune suppression. The most fundamental function of p53 is to serve as an essential growth checkpoint for protecting cells against cellular PB 203580 p38 MAPK inhibitor transformation, thereby resulting in blockage of the cell cycle. The phospho–p53 complex is the active form of p53, and RANTES has chemotactic activity for monocytes/macrophages, T cells, eosinophils, and basophils. In addition, the expression of iNOS increased clearly until day 28 after DEP exposure, whereas that of cyclooxygenase-2 increased until day 14 after DEP exposure. COX-2 is the inducible isoform of COX, which is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. iNOS is the inducible isoform of NOS, which is the enzyme that catalyzes the formation of nitric oxide, a regulator of vascular permeability. Both COX-2 and iNOS are inducible by oxidative stress, and iNOS is inducible by COX-2. p53 also downregulates the angiogenic process at various levels. Furthermore, in this study, all cytokines, except TNF-a and IL12, were measured in the BAL fluid; in particular, the levels of Th2-type cytokines showed a slight increase after DEP exposure until day 14. DEPs were not completely engulfed by immune cells in the BAL fluid until day 14. However, DEPs were absorbed into the blood stream, thereby inducing Th2-type inflammatory responses on day 7 after DEP exposure. The expression of p53, phospho-p53, and TGF-b in lung tissue peaked on day 28, by which time DEPs had been completely engulfed by the immune cells in the BAL fluid. On day 14, a B-cell-dominant trend was absent, despite phagocytosis of DEPs by the immune cells in the BAL fluid and transference of the particles into the blood stream. The ratio of CD4+/CD8+ T cells showed a trend towards greater concentration of CD4+ T cell since day 1, despite the consistent and significant post-treatment increase in the distribution of NK cells expressing markers of CD8+ T cells.