title: Nickel allergy-promoting effects of microbial or inflammatory substances at the sensitization step in mice.
abstract: Microbial components stimulate innate immunity via Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and/or IL-1. We recently reported that in mice, Escherichia coli lipopolysaccharide (LPS, TLR4-ligand) promotes allergic responses to nickel (Ni) at both the sensitization and elicitation steps. Here, we examined in mice the effects of administering other microbial or inflammatory materials at the Ni-sensitization step. A mixture of 1mM NiCl(2) and a test solution was injected into BALB/c mice intraperitoneally (0.1 ml/10 g body weight), and 10 days later 5mM NiCl(2) was challenged intradermally into the ear pinnas of the mice (20 μl/ear). The following preparations or substances exhibited adjuvant activities: Prevotella intermedia LPS, Saccharomyces cerevisiae mannan, a synthetic muramyl dipeptide (NOD2-stimulating cell-wall component of bacteria), Pam(3)Cys-SKKKK (TLR2-stimulating synthetic peptide), poly I:C (TLR3-stimulating double-stranded RNA), concanavalin A (a typical T-cell mitogen and T-cell-mediated hepatitis-inducer), heat-killed Propionibacterium acnes (Gram-positive bacterium that causes pimples and induces macrophage-mediated experimental hepatitis), and nitrogen-containing bisphosphonates (chemicals stimulating IL-1 production). Unexpectedly, P. intermedia LPS, which displayed the most potent adjuvant activity among the tested preparations, was effective in TLR4-dysfunctional mutant mice, but not in TLR2-deficient mice, whereas the reverse was true for S. cerevisiae mannan. These results suggest that (i) for the establishment of Ni-allergy in mice, stimulation of innate immunity (including TLRs, NLRs, IL-1 production, and/or other factors) may be important at the sensitization step, and (ii) P. intermedia may produce a substance(s) that potently promotes Ni-allergy via stimulation of TLR2.
authors.affiliation: Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Harue
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kinbara
authors.forename: Naoki
authors.initials: N
authors.lastname: Sato
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sasaki
authors.forename: Shunji
authors.initials: S
authors.lastname: Sugawara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D003208:Concanavalin A / Q000008:administration & dosage; D004151:Dipeptides / Q000008:administration & dosage; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D007114:Immunization; D018836:Inflammation Mediators / Q000008:administration & dosage; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008074:Lipoproteins / Q000008:administration & dosage; D008351:Mannans / Q000008:administration & dosage; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009532:Nickel / Q000008:administration & dosage*; D011070:Poly I-C / Q000008:administration & dosage; D018713:Prevotella intermedia / Q000276:immunology*; D011425:Propionibacterium acnes / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D004151:Dipeptides; D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008351:Mannans; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D003208:Concanavalin A; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D009532:Nickel; C047210:2,3-bis-(palmitoyloxy)-2-propyl-N-palmitoyl-cysteinylserine; D011070:Poly I-C