Our earlier in vitro and in vivo studies have revealed that the phytosterol, pentalinonsterol (cholest-4,20,24-trien-3-one) (PEN), isolated from the roots of Pentalinon andrieuxii, possesss immunomodulatory properties in macrophages and dendritic cells. Leishmaniasis, caused by the infection of Leishmania spp. (a protozoan parasite), is emerging as the second-leading cause of mortality among the tropical diseases and there is an unmet need for a pharmacological intervention of leishmaniasis. Given the beneficial immunomodulatory actions and lipophilic properties of PEN, the objective of this study was to elucidate the mechanism(s) of action of the immunomodulatory action(s) of PEN in macrophages through the modulation of phospholipase A₂ (PLA₂) activity that might be crucial in the antileishmanial action of PEN. Therefore, in this study, we investigated whether PEN would modulate the activity of PLA₂ in RAW 264.7 macrophages and mouse bone marrow-derived primary macrophages (BMDMs) in vitro and further determined how the upstream PLA₂ activation would regulate the downstream cytokine release in the macrophages. Our current results demonstrated that (i) PEN induced PLA₂ activation (arachidonic acid release) in a dose- and time-dependent manner that was regulated upstream by the mitogen-activated protein kinases (MAPKs); (ii) the PEN-induced activation of PLA₂ was attenuated by the cPLA₂-specific pharmacological inhibitors; and (iii) the cPLA₂-specific pharmacological inhibitors attenuated the release of inflammatory cytokines from the macrophages. For the first time, our current study demonstrated that PEN exhibited its immunomodulatory actions through the activation of cPLA₂ in the macrophages, which potentially could be used in the development of a pharmacological intervention against leishmaniasis.

我们早期的体外和体内研究表明，从Pentalinon andrieuxii的根中分离出来的植物甾醇、pentalinonsterol (cholest-4,20,24-trien-3-one) (PEN)在巨噬细胞和树突状细胞中具有免疫调节特性. 由利什曼原虫感染引起的利什曼病。（一种原生动物寄生虫）正在成为热带疾病中第二大死亡原因，并且对利什曼病的药物干预的需求未得到满足。_{鉴于 PEN 的有益免疫调节作用和亲脂性，本研究的目的是通过调节磷脂酶 A 2} (PLA ₂ ) 阐明 PEN 在巨噬细胞中的免疫调节作用的作用机制) 活动可能对 PEN 的反恶意行为至关重要。因此，在本研究中，我们研究了 PEN 是否会在体外调节RAW 264.7 巨噬细胞和小鼠骨髓来源的原代巨噬细胞 (BMDM) 中 PLA 2 的活性，并进一步确定上游 PLA 2 激活如何_调节下游细胞因子的释放。巨噬细胞。我们目前的研究结果表明，（i）PEN以剂量和时间依赖性方式诱导 PLA _{2活化（花生四烯酸释放），该方式受促分裂原活化蛋白激酶（MAPKs）上游调节；}(ii) cPLA ₂特异性药理学抑制剂减弱了 PEN 诱导的 PLA _2活化；(iii) cPLA_2-特异性药理学抑制剂减弱了巨噬细胞释放炎性细胞因子。我们目前的研究首次证明 PEN 通过激活巨噬细胞中的 cPLA ₂表现出其免疫调节作用，这可能用于开发针对利什曼病的药理学干预措施。