|Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Epidemiology studies demonstrate acute and serious adverse effects of particulate air pollution on cardiorespiratory health especially in the predisposed people susceptible to bacterial infection. We determined the effects of diesel exhaust particles (DEP), major participants in particulate pollutants, on lung injury related to bacterial endotoxin in mice. Intratracheal instillation of DEP synergistically enhanced lung injury related to endotoxin from gram-negative bacteria, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. In the presence of endotoxin, DEP further activated the nuclear translocation of p65 subunit of NF-κ B in the lung, and increased the lung expression of ICAM-1, IL-1 β , macrophage chemoattractant protein-1, KC, macrophage inflammatory protein-1 α , and Toll-like receptors. DEP given alone increased the lung expression of Toll-like receptor 4 and the nuclear localization of p50 subunit of NF-κ B. These results provide the first experimental evidence that DEP enhance neutrophilic lung inflammation related to bacterial endotoxm. The enhancement should be mediated by the induction of proinflammatory molecules likely through the expression of Toll-like receptors and the activation of p65-containing dimer(s) of NF-κ B such as p65/p50 (reference 5).
Furthermore, we have shown DEP or DE enhance airway inflammation related to house dust mite allergen possibly via the enhanced expression of IL-5 and EOTAXIN (reference 6, 9). In another series of experiments, we have demonstrated that DE enhances both immediate and late airway responses as well as mucus secretion (reference 1). In addition, DEP can affect immune systems via the modification of oral tolerance or Th1/Th2 balance (reference 2, 3). Finally, we have demonstrated that nitrogen dioxide in DE can enhance atherogenic metabolic complications especially in obese subjects (submitted).