Tolerance Induced by the Lipopeptide Pam3Cys Is Due to Ablation of IL-1R-Associated Kinase-1

摘要: Stimulation of the human monocytic cell line Mono Mac 6 with synthetic lipopeptide ( S )-(2,3-bis(palmitoyloxy)-(2 RS )-propyl)- N -palmitoyl-( R )-Cys-( )-Ser( )-Lys 4 -OH, trihydrochloride (Pam 3 Cys) at 10 μg/ml induces a rapid expression TNF gene in TLR2-dependent fashion. Preculture cells Pam Cys 1 leads to reduced response after subsequent stimulation μg/ml, indicating that have become tolerant Cys. The CD14 and TLR2 is not decreased on surface cells, but rather up-regulated. Analysis NF-κB binding Cys-tolerant shows failure mobilize NF-κB-p50p65 heterodimers, while NF-κB-p50p50 homodimers remain unchanged. showed neither IκBα-Ser 32 phosphorylation nor IκBα degradation MyD88 protein was unaltered. However, IRAK-1 absent Cys-induced tolerance, mRNA still detectable 30% compared untreated cells. In contrast, LPS-tolerized p50p50 were induced, level only partially decreased, p50p65 mobilization remained intact. It concluded inhibition levels main TLR-2-dependent mechanism responsible for TLR-4-dependent LPS-induced tolerance.