Shepherd V L, Cowan H B, Abdolrasulnia R, Vick S
Department of Medicine, Vanderbilt University, Nashville, Tennessee.
Arch Biochem Biophys. 1994 Aug 1;312(2):367-74. doi: 10.1006/abbi.1994.1321.
The macrophage mannose receptor is highly susceptible to modulation by a variety of proinflammatory and antiinflammatory agents. Previous studies have demonstrated that mannose receptor activity is dramatically increased in rat bone marrow-derived macrophages by dexamethasone treatment and decreased following incubation with interferon-gamma (IFN-gamma). Regulation by both agents occurs at least in part by alteration of mannose receptor mRNA levels. In the present study, we have investigated the ability of dexamethasone to block mannose receptor downregulation in rat marrow macrophages by IFN-gamma. Incubation of rat macrophages with IFN-gamma resulted in downregulation of mannose receptor activity, receptor synthesis, and mRNA levels, with no change in turnover rate of the receptor. IFN-gamma appeared to act at least partially through the generation of nitric oxide: inclusion of the nitric oxide inhibitor N-monomethyl arginine inhibited the IFN-gamma-induced effects on the mannose receptor by approximately 50%. When cells were coincubated with dexamethasone plus IFN-gamma, dexamethasone blocked the decrease in mannose receptor activity, synthesis, and mRNA. Additionally, dexamethasone inhibited nitric oxide production in response to IFN-gamma. These results suggest that mannose receptor expression is downregulated by IFN-gamma by at least two mechanisms: a decrease in mannose receptor mRNA levels and inhibition involving the production of nitric oxide. Dexamethasone has the capability of blocking the effect of IFN-gamma on mannose receptor expression through inhibition of IFN-gamma-mediated downregulation of mannose receptor transcription and/or inhibition of IFN-gamma-mediated induction of nitric oxide production.
巨噬细胞甘露糖受体极易受到多种促炎和抗炎因子的调节。先前的研究表明，地塞米松处理可使大鼠骨髓来源的巨噬细胞中甘露糖受体活性显著增加，而与干扰素-γ（IFN-γ）孵育后则降低。这两种因子的调节至少部分是通过改变甘露糖受体mRNA水平来实现的。在本研究中，我们研究了地塞米松阻断IFN-γ对大鼠骨髓巨噬细胞中甘露糖受体下调作用的能力。用IFN-γ孵育大鼠巨噬细胞导致甘露糖受体活性、受体合成及mRNA水平下调，而受体的周转率无变化。IFN-γ似乎至少部分通过一氧化氮的产生起作用：加入一氧化氮抑制剂N-单甲基精氨酸可使IFN-γ对甘露糖受体的诱导作用降低约50%。当细胞与地塞米松和IFN-γ共同孵育时，地塞米松可阻断甘露糖受体活性、合成及mRNA的降低。此外，地塞米松可抑制IFN-γ诱导的一氧化氮产生。这些结果表明，IFN-γ通过至少两种机制下调甘露糖受体表达：甘露糖受体mRNA水平降低以及涉及一氧化氮产生的抑制作用。地塞米松能够通过抑制IFN-γ介导的甘露糖受体转录下调和/或抑制IFN-γ介导的一氧化氮产生来阻断IFN-γ对甘露糖受体表达的影响。
