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使用白细胞介素-1受体拮抗剂肽来控制炎症，用于治疗角膜缘上皮干细胞缺乏症。

The use of an IL-1 receptor antagonist peptide to control inflammation in the treatment of corneal limbal epithelial stem cell deficiency.

作者信息

Fok E, Sandeman S R, Guildford A L, Martin Y H

机构信息

Biomaterials and Medical Devices Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK ; Blond McIndoe Research Foundation, Queen Victoria Hospital, East Grinstead RH19 3DZ, UK.

Biomaterials and Medical Devices Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.

出版信息

Biomed Res Int. 2015;2015:516318. doi: 10.1155/2015/516318. Epub 2015 Feb 1.

DOI:10.1155/2015/516318
PMID:25705668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4330955/
Abstract

Corneal limbal stem cell deficiency (LSCD) may be treated using ex vivo limbal epithelial stem cells (LESCs) derived from cadaveric donor tissue. However, continuing challenges exist around tissue availability, inflammation, and transplant rejection. Lipopolysaccharide (LPS) or recombinant human IL-1β stimulated primary human keratocyte and LESC models were used to investigate the anti-inflammatory properties of a short chain, IL-1 receptor antagonist peptide for use in LESC sheet growth to control inflammation. The peptide was characterized using mass spectroscopy and high performance liquid chromatography. Peptide cytotoxicity, patterns of cell cytokine expression in response to LPS or IL-1β stimulation, and peptide suppression of this response were investigated by MTS/LDH assays, ELISA, and q-PCR. Cell differences in LPS stimulated toll-like receptor 4 expression were investigated using immunocytochemistry. A significant reduction in rIL-1β stimulated inflammatory cytokine production occurred following LESC and keratocyte incubation with anti-inflammatory peptide and in LPS stimulated IL-6 and IL-8 production following keratocyte incubation with peptide (1 mg/mL) (P < 0.05). LESCs produced no cytokine response to LPS stimulation and showed no TLR4 expression. The peptide supported LESC growth when adhered to a silicone hydrogel contact lens indicating potential use in improved LESC grafting through suppression of inflammation.

摘要

角膜缘干细胞缺乏症（LSCD）可以使用源自尸体供体组织的体外角膜缘上皮干细胞（LESCs）进行治疗。然而，在组织可用性、炎症和移植排斥方面仍然存在持续的挑战。使用脂多糖（LPS）或重组人IL-1β刺激的原代人角膜细胞和LESC模型来研究一种短链IL-1受体拮抗剂肽在LESC片层生长中用于控制炎症的抗炎特性。该肽通过质谱和高效液相色谱进行表征。通过MTS/LDH测定、ELISA和q-PCR研究肽的细胞毒性、细胞对LPS或IL-1β刺激的细胞因子表达模式以及肽对这种反应的抑制作用。使用免疫细胞化学研究LPS刺激下细胞中Toll样受体4表达的差异。在LESC和角膜细胞与抗炎肽孵育后，rIL-1β刺激的炎性细胞因子产生显著减少，并且在角膜细胞与肽（1 mg/mL）孵育后，LPS刺激的IL-6和IL-8产生也显著减少（P < 0.05）。LESC对LPS刺激没有细胞因子反应，并且未显示TLR4表达。当该肽附着在硅水凝胶隐形眼镜上时，它支持LESC生长，表明其通过抑制炎症在改善LESC移植方面具有潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950c/4330955/63631d7a6d57/BMRI2015-516318.010.jpg
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