Laan Lisa C, Williams Andrew R, Stavenhagen Kathrin, Giera Martin, Kooij Gijs, Vlasakov Iliyan, Kalay Hakan, Kringel Helene, Nejsum Peter, Thamsborg Stig M, Wuhrer Manfred, Dijkstra Christine D, Cummings Richard D, van Die Irma
Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands.
Section for Parasitology, Health, and Development, Department of Veterinary Disease Biology, University of Copenhagen, Denmark.
FASEB J. 2017 Feb;31(2):719-731. doi: 10.1096/fj.201600841R. Epub 2016 Nov 2.
Clinical trials have shown that administration of the nematode Trichuris suis can be beneficial in treating various immune disorders. To provide insight into the mechanisms by which this worm suppresses inflammatory responses, an active component was purified from T. suis soluble products (TsSPs) that suppress---- TNF and IL-12 secretion from LPS-activated human dendritic cells (DCs). Analysis by liquid chromatography tandem mass spectrometry identified this compound as prostaglandin (PG)E2. The purified compound showed similar properties compared with TsSPs and commercial PGE2 in modulating LPS-induced expression of many cytokines and chemokines and in modulating Rab7B and P2RX7 expression in human DCs. Furthermore, the TsSP-induced reduction of TNF secretion from DCs is reversed by receptor antagonists for EP2 and EP4, indicating PGE2 action. T. suis secretes extremely high amounts of PGE2 (45-90 ng/mg protein) within their excretory/secretory products but few related lipid mediators as established by metabololipidomic analysis. Culture of T. suis with several cyclooxygenase (COX) inhibitors that inhibit mammalian prostaglandin synthesis affected the worm's motility but did not inhibit PGE2 secretion, suggesting that the worms can synthesize PGE2 via a COX-independent pathway. We conclude that T. suis secretes PGE2 to suppress proinflammatory responses in human DCs, thereby modulating the host's immune response.-Laan, L. C., Williams, A. R., Stavenhagen, K., Giera, M., Kooij, G., Vlasakov, I., Kalay, H., Kringel, H., Nejsum, P., Thamsborg, S. M., Wuhrer, M., Dijkstra, C. D., Cummings, R. D., van Die, I. The whipworm (Trichuris suis) secretes prostaglandin E2 to suppress proinflammatory properties in human dendritic cells.
临床试验表明，给予猪鞭虫（Trichuris suis）对线虫可有助于治疗各种免疫紊乱。为深入了解这种蠕虫抑制炎症反应的机制，从猪鞭虫可溶性产物（TsSPs）中纯化出一种活性成分，该成分可抑制脂多糖激活的人树突状细胞（DCs）分泌肿瘤坏死因子（TNF）和白细胞介素-12（IL-12）。通过液相色谱串联质谱分析确定该化合物为前列腺素（PG）E2。纯化后的化合物在调节脂多糖诱导的多种细胞因子和趋化因子表达以及调节人DCs中Rab7B和P2RX7表达方面，表现出与TsSPs和市售PGE2相似的特性。此外，EP2和EP4受体拮抗剂可逆转TsSP诱导的DCs分泌TNF的减少，表明存在PGE2作用。猪鞭虫在其排泄/分泌产物中分泌极大量的PGE2（45 - 90纳克/毫克蛋白质），但代谢脂质组学分析表明相关脂质介质很少。用几种抑制哺乳动物前列腺素合成的环氧化酶（COX）抑制剂培养猪鞭虫，影响了蠕虫的运动，但不抑制PGE2分泌，这表明蠕虫可通过不依赖COX的途径合成PGE2。我们得出结论，猪鞭虫分泌PGE2以抑制人DCs中的促炎反应，从而调节宿主的免疫反应。 - 拉恩，L.C.，威廉姆斯，A.R.，斯塔芬哈根，K.，吉拉，M.，库伊，G.，弗拉萨科夫，I.，卡莱，H.，克林格尔，H.，内尤姆，P.，坦斯堡，S.M.，武勒尔，M.，迪克斯塔，C.D.，卡明斯，R.D.，范迪，I. 鞭虫（猪鞭虫）分泌前列腺素E2以抑制人树突状细胞中的促炎特性。
