The Journal of immunology (1950), 2004-08, Vol.173 (4), p.2736-2745
2004
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Details
- Autor(en) / Beteiligte
- Titel
- Tolerance Induced by the Lipopeptide Pam3Cys Is Due to Ablation of IL-1R-Associated Kinase-1
- Ist Teil von
- The Journal of immunology (1950), 2004-08, Vol.173 (4), p.2736-2745
- Ort / Verlag
- United States: Am Assoc Immnol
- Erscheinungsjahr
- 2004
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Stimulation of the human monocytic cell line Mono Mac 6 with the synthetic lipopeptide (S)-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys(4)-OH, trihydrochloride (Pam(3)Cys) at 10 microg/ml induces a rapid expression of the TNF gene in a TLR2-dependent fashion. Preculture of the cells with Pam(3)Cys at 1 microg/ml leads to a reduced response after subsequent stimulation with Pam(3)Cys at 10 microg/ml, indicating that the cells have become tolerant to Pam(3)Cys. The CD14 and TLR2 expression is not decreased on the surface of the tolerant cells, but rather up-regulated. Analysis of the NF-kappaB binding in Pam(3)Cys-tolerant cells shows a failure to mobilize NF-kappaB-p50p65 heterodimers, while NF-kappaB-p50p50 homodimers remain unchanged. Pam(3)Cys-tolerant cells showed neither IkappaBalpha-Ser(32) phosphorylation nor IkappaBalpha degradation but MyD88 protein was unaltered. However, IRAK-1 protein was absent in Pam(3)Cys-induced tolerance, while IRAK-1 mRNA was still detectable at 30% compared with untreated cells. In contrast, in LPS-tolerized cells, p50p50 homodimers were induced, IRAK-1 protein level was only partially decreased, and p50p65 mobilization remained intact. It is concluded that in Mono Mac 6 monocytic cells, inhibition of IRAK-1 expression at the mRNA and protein levels is the main TLR-2-dependent mechanism responsible for Pam(3)Cys-induced tolerance, but not for TLR-4-dependent LPS-induced tolerance.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1767eISSN: 1550-6606DOI: 10.4049/jimmunol.173.4.2736Titel-ID: cdi_proquest_miscellaneous_66757814
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing, Antigens, Differentiation - immunology, Antigens, Differentiation - metabolism, Blotting, Western, Cell Line, Fluorescent Antibody Technique, Humans, I-kappa B Proteins - immunology, I-kappa B Proteins - metabolism, Immune Tolerance, Interleukin-1 Receptor-Associated Kinases, Lipopolysaccharide Receptors - immunology, Lipopolysaccharide Receptors - metabolism, Lipopolysaccharides - immunology, Lipopolysaccharides - pharmacology, Lipoproteins - immunology, Lipoproteins - pharmacology, Membrane Glycoproteins - immunology, Membrane Glycoproteins - metabolism, Monocytes - drug effects, Monocytes - immunology, Myeloid Differentiation Factor 88, NF-kappa B - immunology, NF-kappa B - metabolism, NF-KappaB Inhibitor alpha, Protein Kinases - drug effects, Protein Kinases - immunology, Protein Kinases - metabolism, Receptors, Cell Surface - immunology, Receptors, Cell Surface - metabolism, Receptors, Immunologic - immunology, Receptors, Immunologic - metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction - immunology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors, Transfection, Tumor Necrosis Factor-alpha - drug effects, Tumor Necrosis Factor-alpha - immunology, Tumor Necrosis Factor-alpha - metabolism