Department of Pharmacology, College of Medicine, Jeju National University, 66 Jejudaehakno, Jeju, 690-756, South Korea.
J Mol Med (Berl). 2011 Jan;89(1):83-90. doi: 10.1007/s00109-010-0688-0. Epub 2010 Oct 16.
Inflammation as a major defense mechanism against pathogens is modulated by diverse microbial products. A variety of plant and microbial products interacting with Toll-like receptors initiate a wide spectrum of responses from phagocytosis to cytokine production, which modulates inflammation. Jasmonates are fatty acid-derived cyclopentanones produced by plants and lower eukaryotes that play an important role in the defense against insects. In this study, we are set up to define the molecular targets of J2 action. While the lipopolysaccharide (LPS) stimulation of macrophage cell line RAW264.7 induced TNF-α, IL-6, iNOS, and COX-2 that were associated with an increase in miR-155 and miR-146a, the J2 suppressed the induction of these inflammatory cytokines and enzymes as well as miR-155 in a dose-dependent manner. To assess the associations of miR-155 with inflammatory markers, we overexpressed miR-155 and found attenuation of COX-2 suppression with J2 treatment. Furthermore, J2 inhibited NF-κB, p65, and IκB but had no or only minimal effects on the mitogen-activated protein kinase pathway. In conclusion, the present study demonstrates that J2 suppresses LPS stimulation of RAW264.7 cells by targeting NF-κB pathways.
炎症作为一种对抗病原体的主要防御机制，受到多种微生物产物的调节。各种与 Toll 样受体相互作用的植物和微生物产物，引发从吞噬作用到细胞因子产生的广泛反应，从而调节炎症。茉莉酸是植物和低等真核生物产生的脂肪酸衍生的环戊酮，在抵御昆虫方面发挥着重要作用。在这项研究中，我们旨在确定 J2 作用的分子靶标。虽然脂多糖（LPS）刺激巨噬细胞系 RAW264.7 诱导 TNF-α、IL-6、iNOS 和 COX-2，这与 miR-155 和 miR-146a 的增加有关，但 J2 以剂量依赖的方式抑制这些炎症细胞因子和酶以及 miR-155 的诱导。为了评估 miR-155 与炎症标志物的关联，我们过表达了 miR-155，并发现 J2 处理时 COX-2 抑制作用减弱。此外，J2 抑制 NF-κB、p65 和 IκB，但对丝裂原活化蛋白激酶途径没有或只有最小的影响。总之，本研究表明，J2 通过靶向 NF-κB 途径抑制 LPS 刺激的 RAW264.7 细胞。
