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FSL-1 is a synthetic lipopeptide agonist of toll-like receptor 2 (TLR2) and TLR6 heterodimers (TLR2/TLR6). In HEK293 cells transfected with human TLR2 and TLR6 but not TLR6 alone, FSL-1 increases NF-κB activity by 4- and 8-fold when used at concentrations of 0.1 and 1 nM, respectively. It induces the expression of the cytokines CCL20, IL-8, IL-1β, and TNF-α in human monocytic THP-1 cells and, to a lesser extent, in TLR10 knockdown cells when used at a concentration of 100 ng/ml. FSL-1 (0.5-50 μg/ml), in combination with IFN-γ, dose-dependently increases the percentage of DM13 and VMM1 melanoma cells expressing the chemokine CXCL10 with a maximal increase of approximately 50%. In rats, FSL-1 (100 μg/kg, i.p.) induces fever and increases plasma levels of IL-6 and TNF-α by greater than 90-fold. FSL-1 (10-1,000 μg/kg, i.p.) also dose-dependently reduces home cage locomotor activity and both food and water consumption with maximal reductions of ten grams per 12 hours.

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