Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02116, USA.
Ocul Immunol Inflamm. 2009 Nov-Dec;17(6):380-9. doi: 10.3109/09273940903118642.
We have previously found that retinal pigment epithelial (RPE) cells suppressed endotoxin-stimulated macrophages; moreover, it induced expression of anti-inflammatory cytokines. We further assessed the possibility that the RPE is alternatively activating macrophages.
J774A.1 cells were stimulated with endotoxin and treated with the conditioned media (CM) of RPE, or neuroretinal eyecups from healthy mouse eyes. The supernatant was assayed for IL-1 beta, TNF-alpha, IL-6, IL-12(p70), and IL-10, and for nitric-oxide generation. The RPE conditioned media (RPE CM) was absorbed of known soluble factors to identify the factor that augments nitric-oxide generation.
We found the RPE CM suppressed all cytokine production except IL-10, and augmented nitric-oxide generation. The augmented nitric-oxide levels were mediated by RPE derived alpha-melanocyte stimulating hormone (alpha-MSH).
Healthy RPE not only suppresses inflammatory activity, it promotes an alternative activation of macrophages that can further promote immune privilege.
我们之前发现视网膜色素上皮（RPE）细胞可抑制内毒素刺激的巨噬细胞；此外，它还诱导抗炎细胞因子的表达。我们进一步评估了 RPE 细胞可能会使巨噬细胞发生另一种激活的可能性。
用内毒素刺激 J774A.1 细胞，并分别用 RPE 的条件培养基（CM）或来自健康小鼠眼睛的神经视网膜眼杯进行处理。对上清液中的白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-12(p70)（IL-12(p70)）和白细胞介素-10（IL-10）进行检测，并检测一氧化氮（NO）的生成情况。用已知的可溶性因子对 RPE 条件培养基（RPE CM）进行吸收，以鉴定增强 NO 生成的因子。
我们发现 RPE CM 抑制了除 IL-10 以外的所有细胞因子的产生，并增强了 NO 的生成。增强的 NO 水平是由 RPE 衍生的α-促黑素细胞激素（α-MSH）介导的。
健康的 RPE 不仅抑制炎症活性，还促进巨噬细胞的另一种激活，这可以进一步促进免疫豁免。
