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Nano-titanium dioxide modulates the dermal sensitization potency of DNCB

Salik Hussain124, Stijn Smulders2, Vanessa De Vooght2, Bert Ectors2, Sonja Boland1, Francelyne Marano1, Kirsten L Van Landuyt3, Benoit Nemery2, Peter HM Hoet2 and Jeroen AJ Vanoirbeek2*

Author Affiliations

1 Unit of Functional and Adaptive Biology (BFA) CNRS EAC 4413, Laboratory of Molecular and Cellular Responses to Xenobiotics (RMCX), Univ Paris Diderot, Sorbonne Paris Cité, France

2 Department of Public Health, Occupational, Environmental and Insurance Medicine, KU Leuven, Herestraat 49 bus 706, Leuven 3000, Belgium

3 KU Leuven BIOMAT, Department of Oral Health Sciences, Conservative Dentistry, KU Leuven, Leuven, Belgium

4 Present Address: Clinical research unit, National Institute of Environmental Health Sciences (NIEHS)/National Institute of Health (NIH), Research Triangle Park, North Carolina, USA

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Particle and Fibre Toxicology 2012, 9:15  doi:10.1186/1743-8977-9-15

Published: 23 May 2012


We determined the ability of a model nanoparticle (NP) (titanium dioxide, TiO2) to modulate sensitization induced by a known potent dermal sensitizer (dinitrochlorobenzene) using a variant of the local lymph node assay called lymph node proliferation assay.

BALB/c mice received sub-cutaneous injections of vehicle (2.5 mM sodium citrate), TiO2 NPs (0.004, 0.04 or 0.4 mg/ml) or pigment particles (0.04 mg/ml) both stabilized in sodium citrate buffer at the base of each ear (2x50μl), before receiving dermal applications (on both ears) of 2,4-Dinitrochlorobenzene (DNCB) (2x25μl of 0.1%) or its vehicle (acetone olive oil – AOO (4:1)) on days 0, 1 and 2. On day 5, the stimulation index (SI) was calculated as a ratio of 3HTdR incorporation in lymphocytes from DNBC-treated mice and AOO-treated controls. In a second experiment the EC3-value for DNCB (0 to 0.1%) was assessed in the absence or presence of 0.04 mg/ml TiO2. In a third experiment, the lymphocyte subpopulations and the cytokine secretion profile were analyzed after TiO2 (0.04 mg/ml) and DNCB (0.1%) treatment.

Injection of NPs in AOO-treated control mice did not have any effect on lymph node (LN) proliferation. DNCB sensitization resulted in LN proliferation, which was further increased by injection of TiO2 NPs before DNCB sensitization. The EC3 of DNCB, with prior injection of vehicle control was 0.041%, while injection with TiO2 decreased the EC3 of DNCB to 0.015%. TiO2 NPs pre-treatment did not alter the lymphocyte subpopulations, but significantly increased the level of IL-4 and decreased IL-10 production in DNCB treated animals.

In conclusion, our study demonstrates that administration of nano-TiO2 increases the dermal sensitization potency of DNCB, by augmenting a Th2 response, showing the immunomodulatory abilities of NPs.

Nanoparticle; Titanium dioxide (TiO2); Lymph node proliferation assay (LNPA); DNCB; Skin sensitization