作为葡萄糖皮质激素诱导的细胞因子生产调节剂的MIF
T Calandra1, J Bernhagen, C N Metz
1Picower Institute for Medical Research, Manhasset, New York 11030, USA.
Nature
|September 7, 1995
概括
低水平的葡萄糖皮质激素意外地增加了巨细胞迁移抑制因子 (MIF) 的产生. 然后,MIF对抗调节葡萄糖皮质类药物的作用,取代它们的抗炎作用并影响免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 葡萄糖皮质激素对免疫和炎症调节至关重要.
- 现有的知识缺乏内源性调解剂,这些调解剂直接反对葡萄糖皮质激素的作用.
- 巨细胞迁移抑制因子 (MIF) 被认为是一种促炎性细胞因子和败血性休克的媒介.
研究的目的:
- 为了研究葡萄糖皮质体和巨细胞中MIF生产之间的相互作用.
- 为了确定MIF是否可以抵消葡萄糖皮质类药物的免疫抑制作用.
主要方法:
- 用不同度的葡萄糖皮质类药物刺激巨细胞.
- 测量MIF产生的反应在葡萄糖皮质体治疗.
- 评估MIF对单细胞中脂聚糖 (LPS) 诱导的细胞因子分泌的影响.
- 评估MIF对葡萄糖皮质激素介导的对内毒性病的保护的影响.
主要成果:
- 发现低度的葡萄糖皮质类药物可诱导巨细胞产生MIF.
- 观察到MIF会覆盖葡萄糖皮质类药物对LPS刺激单细胞的细胞因子分泌的抑制作用.
- MIF降低了葡萄糖皮质类药物对致命内毒素的保护作用.
结论:
- 已经确定了一种涉及MIF和葡萄皮质激素在免疫反应中的新型反调节系统.
- 这个系统挑战了传统的葡萄皮质激素作用观点,并突出了MIF在调节炎症中的作用.
相关概念视频
Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
Inhaled corticosteroids (ICS) are anti-inflammatory drugs used primarily in treating persistent asthma and providing long-term maintenance. They target the bronchial mucosa, the lining of the airways, to control inflammation, a critical factor in asthma progression and exacerbation.
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel Disease...
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2 (COX-2),...


