FSL-1 TFA

FSL-1 is a synthetic lipopeptide agonist of toll-like receptor 2 (TLR2) and TLR6 heterodimers (TLR2/TLR6).1,2 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.1 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.3 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%.4 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.5 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.
1.Okusawa, T., Fujita, M., Nakamura, J., et al.Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6Infect. Immun.72(3)1657-1665(2004) 2.Farhat, K., Riekenberg, S., Heine, H., et al.Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signalingJ. Leukoc. Biol.83(3)692-701(2008) 3.Le, H.V., and Kim, J.Y.Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine ExpressionInt. J. Mol. Sci.17(6)E859(2016) 4.Mauldin, I.S., Wang, E., Deacon, D.H., et al.TLR2/6 agonists and interferon-gamma induce human melanoma cells to produce CXCL10Int. J. Cancer137(6)1386-1396(2015) 5.HÜbschle, T., MÜtze, J., MÜhlradt, P.F., et al.Pyrexia, anorexia, adipsia, and depressed motor activity in rats during systemic inflammation induced by the Toll-like receptors-2 and -6 agonists MALP-2 and FSL-1Am. J. Physiol. Regul. Integr. Comp. Physiol.290(1)R180-R187(2006)