Abstracts (complete list) - Wissenschaft Online

Julia-Stefanie Frick, Julia Geisel, Frauke Kahl, Hermann Wagner, Carsten Kirschning,
Ingo Autenrieth
IL-6 and maturation govern TLR2 and TLR4 induced TLR
agonist tolerance and cross-tolerance in dendritic cells
Stimulation of murine bone-marrow-derived-dendritic-cells (DC) with lipopolysaccharide
(LPS) or the synthetic lipopeptide N-Palmitoyl-S-[2,3bis(palmitoyloxy)-(2RS)-propyl]-
[R]-cysteinyl-[S]-seryl-[S]-Lys4 x 3 HCl (P3CSK4) induces expression of TNF-a in a
TLR4- and respectively TLR2-dependent fashion. Pre-treatment of DC with LPS results in
hyporesponiveness to a subsequent LPS stimulation, termed LPS-tolerance and to
subsequent P3CSK4 stimulus, termed cross-tolerance. Respectively treatment of DC
with P3CSK4 resulted in homo-tolerance towards subsequent P3CSK4 stimulation as
well as cross-tolerance towards subsequent LPS stimulation. Different mechanism seem
to account for induction of tolerogenic DC. Pre-stimuation with low concentrations of
LPS or P3CSK4 induced tolerogenic DC in an IL-6-dependent fashion and was neither
related to activation and maturation of DC nor to downregulation of TLR2/4 expression.
In contrast, induction of tolerogenic DC by treatment with high concentrations of LPS or
P3CSK4 was independent of IL-6. In homo-tolerogenic DC degradation of IkB was
inhibited, as well as in cross-tolerogenic DC pretreated with high concentration of LPS or
P3CSK4. In contrast, cross-tolerance in DC pretreated with low concentrations of LPS or
P3CSK4 was not related to inhibition of IkB degradation. The data indicate that in DC
TLR4 and TLR2 stimulation results in homo- as well as cross-tolerance and that different
mechanistic effects account for the reduced responsivness of DC.