Atopic dermatitis and skin diseaseStaphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2–Toll-like receptor 6 pathway
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Reagents
The recombinant human cytokines used to stimulate keratinocytes were TNF-α (20 ng/mL), IL-4 (100 ng/mL), IL-13 (100 ng/mL), IFN-γ (100 ng/mL), TGF-β (10 ng/mL), and IL-17A (IL-17; 100 ng/mL; R&D Systems, Minneapolis, Minn). The TLR ligands used to stimulate keratinocytes were (S,R)-(2,3-bispalmitoyloxypropyl)-Cys-Gly-Asp-Pro-Lys-His-Pro-Lys-Ser-Phe (10-1000 ng/mL; (FSL-1; InvivoGen, San Diego, Calif); (S)-[2,3-Bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH, 3HCl (5
Diacylated lipopeptide induced release of TSLP in keratinocytes
We examined whether PGN from S aureus, the synthetic triacylated lipopeptide Pam3CSK4, and the synthetic diacylated lipopeptide FSL-1 induce the release of TSLP. Keratinocytes treated with FSL-1 released detectable amounts of TSLP and IL-8 (Fig 1). PGN and Pam3CSK4 did not induce the release of TSLP at the concentrations tested. Pam3CSK4 induced the release of IL-8 but not TSLP.
The stimulation of keratinocytes with FSL-1 induced the gene (Fig 2, A) or protein (Figs 1 and 2, B) expression of not
Discussion
The human innate immune system recognizes bacterial lipoproteins through TLR2. Some recent reports revealed that, among bacterial products reported as TLR2 agonists, only lipoproteins/lipopeptides are sensed at physiological concentrations by TLR2 and suggested that the TLR2 agonistic activity of the fractions prepared from bacteria, such as PGN and lipoteichoic acid (LTA), is likely due to contaminating, highly active natural lipoproteins/lipopeptides.26, 27, 29, 30 TLR2 forms a heterodimer
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Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to T. T.).
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.