Zamiri Parisa, Masli Sharmila, Streilein J Wayne, Taylor Andrew W
Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3912-8. doi: 10.1167/iovs.05-1267.
To study the contribution of murine retinal pigment epithelial (RPE) cells to the innate immune-privilege status of the subretinal space as determined by the ability of pigment epithelial-derived factor (PEDF) and somatostatin (SOM), produced by RPE, to regulate macrophage-mediated inflammation.
Serum-free medium was added to RPE eyecups (a healthy monolayer of RPE resting on choroid and sclera) and the supernatants were removed after 24 hours (RPE SN). The RPE SN was assayed for the presence of PEDF and SOM and for its ability to regulate interleukin (IL)-12, IL-10, and nitric oxide (NO) production by resting and activated macrophages. A group of mice received intradermal injection of lipopolysaccharide (LPS) and PEDF in one ear and LPS alone in the other ear. Ear thickness was measured before- and 24 hours after ear injections.
Soluble factors present in the RPE SN inhibited IL-12 production and substantially increased IL-10 while having minimal effects on NO production by activated macrophages. The message for PEDF, SOM, and IL-10 was detected in RPE cells, and the protein for these factors was found in the RPE SN. The stimulation of IL-10 and suppression of IL-12 production by RPE-SN-treated macrophages was neutralized by anti-PEDF antibodies. Neutralization of SOM in the RPE SN, suppressed NO production by activated macrophages. Intradermal injection of PEDF substantially inhibited LPS-induced inflammatory response.
PEDF inhibits LPS-driven macrophage activation in vitro and in vivo. By producing PEDF, the RPE contributes to innate immune privilege of the eye.
通过研究视网膜色素上皮（RPE）细胞产生的色素上皮衍生因子（PEDF）和生长抑素（SOM）调节巨噬细胞介导的炎症的能力，探讨小鼠RPE细胞对视网膜下间隙固有免疫豁免状态的作用。
向RPE眼杯（由脉络膜和巩膜支撑的健康单层RPE）中加入无血清培养基，24小时后收集上清液（RPE SN）。检测RPE SN中PEDF和SOM的存在情况，以及其调节静息和活化巨噬细胞产生白细胞介素（IL）-12、IL-10和一氧化氮（NO）的能力。一组小鼠一侧耳皮内注射脂多糖（LPS）和PEDF，另一侧耳仅注射LPS。在注射前和注射后24小时测量耳厚度。
RPE SN中的可溶性因子抑制IL-12的产生，并显著增加IL-10，而对活化巨噬细胞产生NO的影响最小。在RPE细胞中检测到PEDF、SOM和IL-10的信使核糖核酸，在RPE SN中发现这些因子的蛋白质。抗PEDF抗体可中和RPE-SN处理的巨噬细胞对IL-10的刺激和对IL-12产生的抑制。RPE SN中SOM的中和作用抑制了活化巨噬细胞产生NO。皮内注射PEDF可显著抑制LPS诱导的炎症反应。
PEDF在体外和体内均抑制LPS驱动的巨噬细胞活化。RPE通过产生PEDF，有助于眼部的固有免疫豁免。
