title: Involvement of TLR2 and TLR4 and Th1/Th2 shift in inflammatory responses induced by fine ambient particulate matter in mice.
abstract: Epidemiologic studies have reported the association between fine particles (aerodynamic diameter ≤ 2.5 μm; PM2.5) and health effects, but the immunological mechanisms are not clear. To investigate the dose and time-dependent role of toll-like receptor (TLR) and Th1/Th2 shift in local and systemic inflammation induced by PM2.5, mice were subjected to intratracheal instillation of 2.5, 5, or 10 mg/kg PM2.5 in this study. After 24 h, 72 h, 7 days, and 14 days, mice were sacrificed to measure TLR2 and TLR4 expressions and Th1/Th2 related cytokines in bronchoalveolar lavage fluid (BALF) and peripheral blood. Histopathological changes in lung were also examined. Inflammatory infiltration and macrophages with engulfed particles were found by lung histopathology after PM2.5 exposure. TLR4 positive cells decreased in BALF but increased in blood at 24 h after the exposure. The low percentage of TLR4 positive cells continued to day 14 in BALF, but recovered at day 7 and decreased further to lower than the control value at day 14 in blood. TLR2 positive cell changed similar to TLR4 in BALF on the dose effects. In BALF at 24 h after the exposure, the Th2 related cytokines IL-5 and IL-10 increased dose-dependently; and in blood, the Th2 related cytokines IL-4, IL-5, and IL-10 also increased. These results suggest that acute exposure of PM2.5 leads to acute inflammatory responses locally and systemically in mice. TLR2 and TLR4 are involved in this process and PM2.5 can drive a Th2-biased immune response.
authors.affiliation: Department of Respiratory Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhao
authors.forename: Jiping
authors.initials: J
authors.lastname: Liao
authors.forename: Weili
authors.initials: W
authors.lastname: Chu
authors.forename: Suxia
authors.initials: S
authors.lastname: Wang
authors.forename: Tongsheng
authors.initials: T
authors.lastname: Yang
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tao
authors.forename: Guangfa
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D052638:Particulate Matter; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4