title: Nano-titanium dioxide modulates the dermal sensitization potency of DNCB.
abstract: We determined the ability of a model nanoparticle (NP) (titanium dioxide, TiO(2)) 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), TiO(2) 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 (3)HTdR incorporation in lymphocytes from DNBC-treated mice and AOO-treated controls. In a second experiment the EC(3)-value for DNCB (0 to 0.1%) was assessed in the absence or presence of 0.04 mg/ml TiO(2). In a third experiment, the lymphocyte subpopulations and the cytokine secretion profile were analyzed after TiO(2) (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 TiO(2) NPs before DNCB sensitization. The EC(3) of DNCB, with prior injection of vehicle control was 0.041%, while injection with TiO(2) decreased the EC(3) of DNCB to 0.015%. TiO(2) 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-TiO(2) increases the dermal sensitization potency of DNCB, by augmenting a Th(2) response, showing the immunomodulatory abilities of NPs.
authors.affiliation: Unit of Functional and Adaptive Biology CNRS EAC 4413, Laboratory of Molecular and Cellular Responses to Xenobiotics, Univ Paris Diderot, Sorbonne Paris Cité, France.
authors.forename: Salik
authors.initials: S
authors.lastname: Hussain
authors.forename: Stijn
authors.initials: S
authors.lastname: Smulders
authors.forename: Vanessa
authors.initials: V
authors.lastname: De Vooght
authors.forename: Bert
authors.initials: B
authors.lastname: Ectors
authors.forename: Sonja
authors.initials: S
authors.lastname: Boland
authors.forename: Francelyne
authors.initials: F
authors.lastname: Marano
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Van Landuyt
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Vanoirbeek
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000494:pharmacology; D004431:Ear, External / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D007509:Irritants / Q000008:administration & dosage / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D014025:Titanium / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D004137:Dinitrochlorobenzene; D007155:Immunologic Factors; D007509:Irritants; C009495:titanium dioxide; D014025:Titanium