title: Adjuvant effect of lipopolysaccharide on the induction of contact hypersensitivity to haptens in mice.
abstract: BACKGROUND
  Toll-like receptor (TLR) 4 is a critical receptor and signal transducer for lipopolysaccharide (LPS), a major component of Gram-negative bacteria. The MyD88-independent pathway downstream of TLR4 leads to functional dendritic cell (DC) maturation, although LPS-induced cytokine production from DCs is MyD88-dependent.
  
  
  OBJECTIVE
  We investigated whether intracutaneously injected LPS alters the functions of cutaneous DCs, leading to enhanced contact hypersensitivity (CH).
  
  
  METHODS
  The ear swelling response was measured to evaluate the magnitude of CH. Cell proliferation of allogeneic splenocytes stimulated by DC-enriched draining lymph node (LN) cells was measured by performing a [(3)H]-thymidine incorporation assay. Epidermal I-A+ cells were evaluated under an epifluorescent microscope. I-A+ FITC-bearing cells from the draining LNs 24h after FITC application were analyzed on FACScan.
  
  
  RESULTS
  LPS augmented CH induction in C3H/HeN (HeN) and MyD88-knockout (KO) mice but not in C3H/HeJ (HeJ) and H-2S(d)-bearing strains such as BALB/c mice. LPS failed to augment the allo-stimulatory ability of DCs in the draining LNs after hapten applications. LPS altered the density and morphology of epidermal I-A+ cell in HeN and BALB/c mice but not in TLR4-deficient HeJ mice. LPS increased the proportion of I-A+ FITC-bearing cells in the LNs 24h after FITC application in HeN, but not in BALB/c and HeJ.
  
  
  CONCLUSIONS
  LPS augments the ability of DCs to migrate to the draining LNs, leading to enhanced CH via a TLR4-dependent, MyD88-independent pathway. The different effects of LPS on CH in some strains of mice may explain individual differences in the susceptibility to establish CH to daily antigen exposures in clinical settings.
authors.affiliation: Department of Dermatology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Yokoi
authors.forename: Hironori
authors.initials: H
authors.lastname: Niizeki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Iida
authors.forename: Hideo
authors.initials: H
authors.lastname: Asada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyagawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene; D004195:Disease Models, Animal; D006183:H-2 Antigens / Q000378:metabolism; D006241:Haptens; D007271:Injections, Intradermal; D007801:Langerhans Cells / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D013045:Species Specificity; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D006183:H-2 Antigens; D006241:Haptens; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C433788:lipopolysaccharide, E. coli O26-B6; D004139:Dinitrofluorobenzene