sPLA2-IIa amplifies ocular surface inflammation in the experimental dry eye (DE) BALB/c mouse model.
sPLA2-IIa amplifies ocular surface inflammation in the experimental dry eye (DE) BALB/c mouse model.
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DOI：
10.1167/iovs.10-6350
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发表时间：
2011-07
影响因子：
4.4
通讯作者：
Yi Wei;S. Epstein;S. Fukuoka;N. Birmingham;Xiu-Min Li;P. Asbell
中科院分区：
文献类型：
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作者：
Yi Wei;S. Epstein;S. Fukuoka;N. Birmingham;Xiu-Min Li;P. Asbell
目的sPLA 2-IIa是人类许多炎症性疾病的生物标志物，在人类泪液中含量很高。然而，其在眼表炎症中的作用仍不清楚。采用BALB/c小鼠干眼症（dry eye，DE）模型，观察sPLA 2-IIa在眼表炎症中的作用。方法BALB/c小鼠皮下注射东莨菪碱，置于日间空气干燥装置中5 ~ 10 d。对照小鼠不接受治疗。DE状态通过用酚红线法产生的泪液进行评估。泪液炎性细胞因子通过多重免疫测定进行定量。免疫组化染色和定量RT（2）-PCR检测眼表炎症和sPLA 2-IIa表达。培养小鼠结膜（CNJ），用于由sPLA 2-IIa与不同量的sPLA 2-IIa抑制剂S-3319诱导的前列腺素E2产生。结果与对照组相比，治疗组小鼠泪液分泌减少，角膜荧光素染色加深（P < 0.001）。与对照组相比，他们还显示出较低的杯状细胞密度（P < 0.001），结膜内的炎性细胞浸润更大，泪液炎性细胞因子的浓度更高。此外，治疗组小鼠CNJ上皮中的sPLA 2-IIa免疫染色比对照组重，但CN上皮或泪腺中的sPLA 2-IIa免疫染色不重。经治疗的小鼠表现出sPLA 2-IIa和细胞因子基因转录的上调。此外，用sPLA 2-IIa抑制剂处理的CNJ培养物显示出显著减少的sPLA 2-IIa诱导的炎症。结论：这是首次报道sPLA 2-IIa对眼表炎症的调节作用。因此，这些发现可能会导致眼表炎症，如DE疾病的新的治疗策略。
PURPOSE sPLA2-IIa is a biomarker for many inflammatory diseases in humans and is found at high levels in human tears. However, its role in ocular surface inflammation remains unclear. An experimentally induced BALB/c mouse dry eye (DE) model was used to elucidate the role of sPLA2-IIa in ocular surface inflammation. METHODS BALB/c mice were subcutaneously injected with scopolamine and placed in a daytime air-drying device for 5 to 10 days. Control mice received no treatment. DE status was evaluated with tear production with a phenol-red thread method. Tear inflammatory cytokines were quantified by multiplex immunoassays. Ocular surface inflammation and sPLA2-IIa expression were examined by immune-staining and quantitative (q)RT(2)-PCR. Conjunctiva (CNJ) of the mice was cultured for prostaglandin E2 production induced by sPLA2-IIa with various amount of sPLA2-IIa inhibitor, S-3319. RESULTS Treated mice produced fewer tears and heavier corneal (CN) fluorescein staining than the untreated controls (P < 0.001). They also revealed lower goblet cell density (P < 0.001) with greater inflammatory cell infiltration within the conjunctiva, and higher concentration of tear inflammatory cytokines than the controls. Moreover, treated mice showed heavier sPLA2-IIa immune staining than the controls in the CNJ epithelium, but not in the CN epithelium or the lacrimal gland. Treated mice exhibited upregulated sPLA2-IIa and cytokine gene transcription. Furthermore, CNJ cultures treated with sPLA2-IIa inhibitor showed significantly reduced sPLA2-IIa-induced inflammation. CONCLUSIONS This is the first report regarding sPLA2-IIa in the regulation of ocular surface inflammation. The findings may therefore lead to new therapeutic strategies for ocular surface inflammation, such as DE disease.