Diesel exhaust (DE) aggravates pathology of delayed-type hypersensitivity (DTH) induced by methyl-bovine serum albumin (mBSA) in mice.
Diesel exhaust particles (DEP), a well-known air pollutant, exacerbate type I hypersensitivity conditions, such as asthma and pollen allergy. In this study, we examined the effect of diesel exhaust (DE) exposure on delayed-type hypersensitivity (DTH), a type IV hypersensitivity, induced with methyl-bovine serum albumin (mBSA) in C57BL/6 mice. Mice were exposed to DE containing DEP at a dose of 1.78 mg/m(3) in an inhalation chamber for 14 days. On Day 7, DTH mice and DE-exposed DTH mice were injected s.c. with 200 microl of 1.25 mg/ml mBSA emulsified with CFA in the dorsal region as initial sensitization. On Day 14, mice were injected s.c. into one footpad with 20 microl of 10 mg/ml mBSA dissolved in PBS as challenge. On Day15, footpad thickness and spleen weight were measured. Significant footpad swelling (%) was observed in DTH mice compared with normal control mice, and this swelling was significantly augmented by DE exposure. The levels of pro-inflammatory cytokines, including IFN-gamma, TNF-alpha, and IL-6, in DTH mice were significantly higher than in normal mice, and were also further enhanced by DE exposure. DE exposure increased production of IL-17, which enhances local tissue inflammation through up-regulation of pro-inflammatory cytokines, while production of IL-10, which inhibits local tissue inflammation through suppression of immune cell proliferation, was unchanged. No change was observed in the percentage of CD4(+)CD25(+)Foxp3(+)T regulatory (Treg) cells in splenic lymphocytes following DE exposure. IL-6 production was increased by DE, and this would facilitate the differentiation of naïve T cells to IL-17-producing Th17 cells, while concomitantly suppressing the competing differentiation pathway to IL-10-producing Treg cells. Our results indicate that DE inhalation may, in part, exacerbate the pathological symptoms of DTH and induction of pro-inflammatory cytokines such as IFN-gamma, TNF-alpha, IL-6 and IL-17.
Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS) Noda-shi, Chiba, Japan.
Masanobu
M
Sakai
Keichiro
K
Yamashita
Naoya
N
Takemoto
Yasuhiro
Y
Ohshima
Mitsutoshi
M
Tsukimoto
Yusuke
Y
Shinkai
Ken
K
Takeda
Shigeru
S
Oshio
Shuji
S
Kojima
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D012710:Serum Albumin, Bovine / Q000276:immunology*; D013163:Splenomegaly / Q000175:diagnosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
D016207:Cytokines; D020381:Interleukin-17; D015850:Interleukin-6; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma