Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse

Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse
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DOI:
10.1136/bjo.2005.084525
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发表时间:
2006-05-01
影响因子:
4.1
通讯作者:
Herlyn, M
Herlyn, M
中科院分区:
医学2区
文献类型:
--
作者:
Oka, M;Norose, K;Herlyn, M

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目的:虽然白细胞介素8(IL-8)在正常角膜中不产生,但在几种病理条件下已检测到。方法:将IL-8/Ad 5重组腺病毒感染重症联合免疫缺陷小鼠角膜,观察不同时间点的临床和病理变化。在组织学上,在12小时时在角膜基质中观察到显著的血管生成。在16小时时观察到角膜上皮和基质之间的裂隙形成,以及中性粒细胞浸润到角膜基质中。在用IL-8/Ad 5感染后24小时,在角膜中形成浅溃疡。相比之下,感染对照腺病毒携带β半乳糖苷酶基因(LacZ)既没有角膜溃疡,也没有中性粒细胞浸润。免疫组化分析表明,感染IL-8/Ad 5导致IL-8的生产由角膜和结膜基质cells.Conclusion:我们的研究结果表明,IL-8在角膜组织中的过度表达,导致溃疡的形成,通过中性粒细胞的化学吸引,提示IL-8在某些类型的角膜溃疡的病因作用。
Aims: Although interleukin 8 (IL-8) is not produced in the normal cornea, it has been detected there in several pathological conditions. In this study, the direct effects of IL-8 overexpression on the cornea was examined.Methods: The corneal surface of severe combined immunodeficiency mice was infected by the adenovirus vector encoding human IL-8 (IL-8/Ad5) and clinical and pathological changes were observed at various time points.Results: Clinically, marked angiogenesis and ulcer formation in the cornea were observed by 12 hours and 24 hours, respectively. Histologically, prominent angiogenesis was observed in the corneal stroma at 12 hours. Cleft formation between the corneal epithelium and stroma, and neutrophil infiltration into the corneal stroma were seen at 16 hours. By 24 hours after the infection with IL-8/Ad5, a shallow ulcer was formed in the cornea. In contrast, infection with the control adenovirus carrying the beta galactosidase gene (LacZ) showed neither corneal ulceration nor neutrophil infiltration. Immunohistochemical analysis showed that infection with IL-8/Ad5 resulted in the production of IL-8 by corneal and conjunctival stromal cells.Conclusion: Our results indicate that IL-8 overexpression in corneal tissue causes ulcer formation in the cornea through chemoattraction of neutrophils, suggesting the aetiological role of IL-8 in some types of corneal ulcers.