在飲食中做為一個重要的微量元素，硒 (Se) 在哺乳動物各種生理功能當中扮演著重要的角色，穀胱甘肽過氧化物酶（Se-GPx）和硫氧化還原蛋白還原酶 (thioredoxin reductase) 是較為人所熟知具有特色的硒酶成員，而他們的活化需要硒 (Se) 來參與。在此，我們試圖研究硒 (Se) 對巨噬細胞的影響，以及去觀測其與TLR-mediated signaling的關係。在本論文中，我們探討硒 (Se) 是否會降低LPS誘導巨噬細胞的移行能力，同時使用了PP2 ( Src family kinase (SFKs)的抑制劑) 來觀察其共同作用。在巨噬細胞培養液中添加硒 (Se)的情況下會降低酯多醣Lipopolysaccharide (LPS;內毒素) 誘導巨噬細胞總體酪氨酸磷酸化的增加。接著分析SFK成員蛋白表現的情形，結果發現巨噬細胞生長在添加硒 (Se) 的培養液時，LPS誘導 Src 的表現量會下降，但對myeloid SFKs (如Lyn、Fgr、Hck) 的蛋白表現量則不見有什麼影響。值得注意的是，RAW264.7細胞用RNA interference 的技術減少Src的表現量，會降低LPS增加FAK Pi-Tyr861 (FAK-pY861) 的量，減弱LPS誘發的細胞移行能力；而恢復Src蛋白量時，則可恢復這些情況。而硒 (Se) 都能夠有效降低此現象。綜合上述的結果，我們認為硒 (Se) 可以降低LPS誘導下的Src表現，進而影響巨噬細胞的移行能力。
As an essential micronutrient in diet, selenium (Se) is critical in a variety of physiological functions in mammals. Glutathione peroxidase (Se-GPx) and thioredoxin reductase families are the most well characterized selenoenzymes whose activation requires the participation of Se. Here, we attempted to study the effect of Se and searched for its targets in Toll–Like receptor (TLR) -mediated signaling pathways. In this study, we observed that Se supplement reduced LPS-mediated macrophage motility, which was PP2 (an inhibitor for Src family kinase (SFKs)) sensitive. Consistently, Se supplement also decreased total phosphotyrosine content in LPS-exposed macrophages. Analysis of the expression of SFKs, we observed that Se supplement attenuated LPS-induced Src expression while the amount of its myeloid relatives (i.e. Lyn, Fgr and Hck) was almost unaltered. Remarkably, attenuation of Src suppressed Se-exerted decrement of LPS-mediated macrophage mobilization and the level of FAK Pi-Tyr861, which could be reversed by the reintroduction of siRNA-resistant src. With these findings, we concluded that by
suppressing the induction of Src, Se could effectively inhibit LPS-evoked macrophage motility.
