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Abstract：
Cystatins are natural inhibitors of cysteine peptidases that are found practically in all living organisms. CaneCPI-5 is a sugarcane cystatin with inhibitory activity against human cathepsins B, K and L, which are cysteine proteases highly expressed in a variety of pathological conditions, usually marked by persistent inflammation and processing of the extracellular matrix. This work evaluated the effects of daily administration of the recombinant cystatin CaneCPI-5 [0.01, 0.1 or 1.0 μg in 10 μL of Phosphate-Buffered Saline (PBS)] on the inflammatory, angiogenic and fibrogenic components during chronic inflammatory response induced by subcutaneous sponge implants. The anti-inflammatory effect of treatment with CaneCPI-5 was confirmed by reduction of the levels of the pro-inflammatory mediators TNF-α, CXCL1 and CCL2/JE/MCP-1, as well as the activity of the myeloperoxidase and n-acetyl-β-D-glucosaminidase. Treatment with CaneCPI-5 promoted angiogenesis in the implants, increasing the production of cytokines VEGF and FGF and the formation of new blood vessels. Finally, the administration of the recombinant cystatin favored the production of the pro-fibrogenic cytokine TGF-β1 and collagen deposition next to the implants. Together, these results show the potential therapeutic application of CaneCPI-5 as an anti-inflammatory agent, capable of favoring angiogenesis and fibrogenesis processes, necessary for tissue repair.
摘要：
胱抑素是几乎在所有活生物体中发现的半胱氨酸肽酶的天然抑制剂。CaneCPI-5是一种对人类组织蛋白酶B具有抑制活性的甘蔗胱抑素，K和L,半胱氨酸蛋白酶是在多种病理条件下高度表达的，通常以持续的炎症和细胞外基质的处理为标志。这项工作评估了每天施用重组胱抑素CaneCPI-5[在10μL磷酸盐缓冲盐水（PBS）中0.01、0.1或1.0μg]对炎症的影响，皮下海绵植入物诱导的慢性炎症反应期间的血管生成和纤维化成分。通过降低促炎介质TNF-α的水平证实了用CaneCPI-5治疗的抗炎作用。CXCL1和CCL2/JE/MCP-1，以及髓过氧化物酶和n-乙酰-β-D-氨基葡萄糖苷酶的活性。用CaneCPI-5治疗促进植入物中的血管生成,增加细胞因子VEGF和FGF的产生以及新血管的形成。最后,重组胱抑素的施用有利于促纤维化细胞因子TGF-β1的产生和植入物旁边的胶原沉积。一起,这些结果表明CaneCPI-5作为抗炎剂的潜在治疗应用，能够促进血管生成和纤维发生过程，组织修复所必需的。
