Kaszowska Marta, Wojcik Marta, Siednienko Jakub, Lugowski Czeslaw, Lukasiewicz Jolanta
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Department of Biotechnology and Molecular Biology, University of Opole, Opole, Poland.
Front Immunol. 2017 Dec 11;8:1741. doi: 10.3389/fimmu.2017.01741. eCollection 2017.
is a Gram-negative bacterium that is associated with diarrheal disease in humans. Lipopolysaccharide (LPS) is the main surface antigen and virulence factor of this bacterium. The lipid A (LA) moiety of LPS is the main region recognized by target cells of immune system. Here, we evaluated the biological activities of LA for their abilities to induce the productions of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) by human and murine macrophages [THP-1 macrophages and immortalized murine bone marrow-derived macrophages (iBMDM)]. Four native LA preparations differing in their phosphoethanolamine (PEtn) substitution, length, number, and saturation of fatty acids were compared with O55 LA. The bisphosphorylated, hexaacylated, and asymmetric forms of the and LA molecules had similar activities in human and murine macrophages, indicating that shortening of the acyl chains in LA had no effect on its activities. The PEtn decoration also had no impact on the interaction with the toll-like receptor 4/MD-2 receptor complex. The heptaacylated form of LA decorated with 16:0 exhibited strong effect on proinflammatory activity, significantly decreasing the levels of all tested cytokines in both murine and human macrophages. Our results revealed that despite the presence of shorter acyl chains and an unsaturated acyl residue (16:1), the bisphosphorylated, hexaacylated, and asymmetric forms of LA represent highly immunostimulatory structures.
是一种与人类腹泻疾病相关的革兰氏阴性菌。脂多糖（LPS）是该细菌的主要表面抗原和毒力因子。LPS的脂质A（LA）部分是免疫系统靶细胞识别的主要区域。在此，我们评估了LA的生物活性，以其诱导人和鼠巨噬细胞[THP-1巨噬细胞和永生化鼠骨髓来源的巨噬细胞（iBMDM）]产生促炎细胞因子（TNF-α、IL-1β和IL-6）的能力来衡量。将四种在磷酸乙醇胺（PEtn）取代、脂肪酸长度、数量和饱和度方面不同的天然LA制剂与O55 LA进行了比较。LA分子的双磷酸化、六酰化和不对称形式在人和鼠巨噬细胞中具有相似的活性，这表明LA中酰基链的缩短对其活性没有影响。PEtn修饰对与Toll样受体4/MD-2受体复合物的相互作用也没有影响。用16:0修饰的七酰化形式的LA对促炎活性有强烈影响，显著降低了鼠和人巨噬细胞中所有测试细胞因子的水平。我们的结果表明，尽管存在较短的酰基链和一个不饱和酰基残基（16:1），LA的双磷酸化、六酰化和不对称形式仍代表高度免疫刺激结构。
