A Udomratana Vattanasit creator Mathuros Ruchirawat Chairperson Autrup, Herman Co-Chairperson Visvanathan, C. Co-Chairperson Preeda Pakpian Examination Committee Gallardo, Wenresti G. Examination Committee Panida Navasumrit Examination Committee Chulabhorn Research Institute Scholarship Donor Mahidol University Scholarship Donor text th Pathum Thani Asian Institute of Technology 2013 monographic eng 1 online resource (127 p.) : ill. Particulate air pollution is a major public health concern because epidemiological studies have demonstrated that exposure to particulate matter (PM) is associated with health effects such as respiratory diseases and lung cancer. Diesel exhaust particles (DEP) are considered a major contributor to the particulate air pollution in urban areas. DEP consists of various compounds, including polycyclic aromatic hydrocarbons (PAHs) and metalswhich are the principal components that contribute to the toxicity of PM. The present study aimed to investigate effects of PM on induction of inflammation by using lymphocytes in vitro and in human exposed to PM in the environment. Human lymphoblasts (RPMI 1788)were treated with a reference DEP (SRM 2975) at various concentrations (25-100 og/ml) to compare the extent of oxidative stress and inflammatory responses with alveolar epithelial cells (A549). The oxidative response was determined by formation of reactive oxygen species (ROS) whereas the inflammatory responses were assessed by the change in expression of interleukin-6 and -8 (IL-6 and IL-8), Clara cell protein (CC16), and lung surfactant protein-A and -D (SP-A and SP-D). In addition, a human study was conducted in 51 healthy subjects residing in traffic-congested areas in Bangkok, including Dindaeng and Pradipat. Ambient and individual exposure concentrations of respirable particles (PM2.5) and their chemical components, including PAHs and metals, were measured. Circulating lymphocytes and serum from the subjects were assessed for the inflammatory responses.The results show that DEP was internalized and preferentially induced ROS generation in G2/M phase in both A549 and RPMI 1788 cells in a dose-dependent manner. Moreover, DEP up- regulated the expression of pro-inflammatory cytokines genes (IL-6 and IL-8) in both cell types but down-regulated the expression of anti-inflammatory protein gene(CC16) in A549 cells. The response in RPMI 1788 cells was faster than in A549 cells, and is most likely due to a rapid uptake of the particles. The inflammatory responses were similar in A549 and RPMI1788 cells, and IL-8expression was the most sensitive parameter. The mean ambient and individual exposure concentrations of PM2.5 in the two locations were not significantly different while individual exposure concentrations of PAHs in Dindaeng were significantly higher (P < 0.001). Indeno[c,d]pyrene was the predominant PAH in the two locations suggesting that traffic is the major source of the particles. As and Pb were metals commonly found in the particles from both locations. IL-8expression in the lymphocyte was not correlated with the individual exposure concentrations of PM2.5 and its chemical components. However, the concentrations of serum CC16 showed significant negative correlations with benzo[k] fluoranthene, benzo[a]pyrene, and dibenzo[a,h]anthracene and a significant positive correlation with Pb (P < 0.05). Significantly higher concentrations of exposure to PAHs and lower concentrations of serum CC16 of subjects in Dindaeng (P < 0.01) suggest that the particle-bound PAHs might decrease CC16 production in the lung. In conclusion, A549 and RPMI 1788 cells had a similar pattern of dose-dependent responses in terms of DEP uptake, ROS generation, and induction of the pro-inflammatory cytokine gene expression. The circulating lymphocyte represented by RPMI 1788 cells could be used as a surrogate in assessing PM-induced inflammatory responses in the lung. The human results indicate that PM-induced inflammation was not conclusive and should be further investigated, while a decreased level of serum CC16 may be observed in healthy people exposed to traffic-related particles in the ambient environment. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Environmental Engineering and ManagementInter-University Program on Environmental Toxicology, Technology and Management Thesis (Ph.D.) - Asian Institute of Technology - Chulabhorn Research Institute - Mahidol University, 2013 Particles Environmental aspects Air Pollution Asian Institute of Technology. http://203.159.5.9/ait-thesis/detail.php?q=B00573 http://203.159.5.9/ait-thesis/detail.php?q=B00573 140611 20260818223113.0