FSL-1 is a synthetic diacyl lipopeptide TLR2/6 agonist [1]. FSL-1 binds to and activates TLR2/6 heterodimers, triggering downstream MyD88-dependent signaling pathways, leading to activation of NF-κB, MAPK, and other pathways, and inducing the release of multiple inflammatory factors (TNF-α, IL-1β, IL-6, IL-8) and chemokines [2-3]. FSL-1 is primarily used in immunology and inflammation research [4].
In THP-1 cells, FSL-1 (50ng/mL; 24h) induces MMP-9 gene expression [5]. In HaCaT cells, FSL-1 (100ng/mL; 0.5-2h) stimulation downregulates TGB6 expression [6].
In radiation mice model, prophylactic administration of FSL-1 (0.25mg/kg; sc; 40d) significantly improves the survival rate of male and female C57BL/6 mice [7]. In radiation mice model, FSL-1 (0.09mg/kg; sc; 8d) stimulates the recruitment of hematopoietic progenitor cells [8].
References:
[1]. Rose W A, McGowin C L, Pyles R B. FSL-1, a bacterial-derived toll-like receptor 2/6 agonist, enhances resistance to experimental HSV-2 infection[J]. Virology journal, 2009, 6(1): 195.
[2]. Kurkjian C J, Guo H, Montgomery N D, et al. The toll–like Receptor 2/6 agonist, FSL–1 lipopeptide, therapeutically mitigates acute radiation syndrome[J]. Scientific Reports, 2017, 7(1): 17355.
[3]. Nakamura J, Shibata K, Hasebe A, et al. Signaling pathways induced by lipoproteins derived from Mycoplasma salivarium and a synthetic lipopeptide (FSL‐1) in normal human gingival fibroblasts[J]. Microbiology and immunology, 2002, 46(3): 151-158.
[4]. Lim R, Barker G, Lappas M. The TLR 2 Ligand FSL‐1 and the TLR 5 Ligand Flagellin Mediate Pro‐Inflammatory and Pro‐Labour Response via MyD88/TRAF 6/NF‐κB‐Dependent Signalling[J]. American Journal of Reproductive Immunology, 2014, 71(5): 401-417.
[5]. Ahmad R, Shihab P K, Jasem S, et al. FSL-1 induces MMP-9 production through TLR-2 and NF-κB/AP-1 signaling pathways in monocytic THP-1 cells[J]. Cellular Physiology and Biochemistry, 2014, 34(3): 929-942.
[6]. Xu M, Huang J, Zhu F, et al. FOXO1 inhibits FSL-1 regulation of integrin β6 by blocking STAT3 binding to the integrin β6 gene promoter[J]. Frontiers in Cellular and Infection Microbiology, 2022, 12: 998693.
[7]. Holmes-Hampton G P, Kumar V P, Valenzia K, et al. FSL-1: A Synthetic Peptide Increases Survival in a Murine Model of Hematopoietic Acute Radiation Syndrome[J]. Radiation Research, 2024, 201(5): 449-459.
[8]. Brickey W J, Caudell D L, Macintyre A N, et al. The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates[J]. Proceedings of the National Academy of Sciences, 2023, 120(50): e2122178120.
FSL-1是一种合成的二酰基脂肽TLR2/6激动剂 [1]。FSL-1结合并激活TLR2/6异二聚体，触发下游MyD88依赖性信号通路，进而激活NF-κB、MAPK等通路，诱导多种炎症因子（TNF-α、IL-1β、IL-6、IL-8）和趋化因子的释放 [2-3]。FSL-1主要用于免疫学和炎症研究 [4]。
在THP-1细胞中，FSL-1（50ng/mL；24h）可诱导MMP-9基因表达 [5]。在HaCaT细胞中，FSL-1（100ng/mL；0.5-2h）刺激可下调TGB6表达 [6]。
在辐射小鼠模型中，预防性给予FSL-1（0.25mg/kg；sc；40d）显著提高了雄性和雌性C57BL/6小鼠的存活率 [7]。在辐射小鼠模型中，FSL-1（0.09mg/kg；sc；8d）刺激造血祖细胞的募集 [8]。