Retina Service, Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
Invest Ophthalmol Vis Sci. 2012 Jun 28;53(7):4158-69. doi: 10.1167/iovs.11-9323.
To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU).
C57BL/6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-γ, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-Ab) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured.
AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression.
AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR.
研究腺嘌呤单核苷酸（AMP）类似物氨基咪唑羧酰胺核苷酸（AICAR）在实验性自身免疫性葡萄膜炎（EAU）中的抗炎作用。
C57BL/6 小鼠从 0 天（即光感受器间视网膜结合蛋白 [IRBP] 免疫的当天）开始每天腹腔内（IP）注射 AICAR（200mg/kg），直至第 21 天。通过临床和组织病理学评估葡萄膜炎的严重程度。测定 T 细胞增殖和 IFN-γ、IL-17 和 IL-10 对 IRBP 刺激的细胞因子产生。此外，还测量了调节性 T 细胞（Treg）群体。测量 EAU 中树突状细胞（DC）和用 AICAR 处理的骨髓来源的树突状细胞（BMDC）上共刺激分子表达（CD40、80、86 和 I-Ab）。
AICAR 治疗显著减轻 EAU 的临床和组织学严重程度以及眼内细胞因子产生。观察到与 T 细胞增殖和 Th1 和 Th17 细胞因子产生抑制相关的抗炎作用。AICAR 治疗未观察到 Th2 反应和 Treg 群体增加。AICAR 通过降低共刺激分子表达显著抑制 BMDC 成熟。
AICAR 通过防止 Ag 特异性 Th1 和 Th17 细胞的产生来减轻 EAU。受损的 DC 成熟可能是 AICAR 观察到的这种抗炎作用的潜在机制。
