Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University, 221 Huksuk-dong, Dongjak-gu, Seoul 156–756, South Korea.
Biol Pharm Bull. 2013;36(3):425-31. doi: 10.1248/bpb.b12-00869.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important regulator of the maturation and function of cells in the granulocyte and macrophage lineages, and also plays a significant role in wound healing. In a previous study, we expressed human GM-CSF in rice cells (rice cell-derived human GM-CSF; rhGM-CSF). The purpose of the present study was to evaluate its effect on wound healing in oral mucositis. Oral mucositis was induced in Syrian hamster cheek pouches by 5-fluorouracil treatment and mechanical scratching. Ulcerated areas were treated from days 3 to 14 with an application of 200 µL saline, or of the same volume of a solution containing 0.04, 0.2, or 1 µg/mL rhGM-CSF. Treatment of hamsters with rhGM-CSF reduced the ulcerated areas of the oral mucosa, compared with the control. Early in the healing process, the mucositis tissue layer of the rhGM-CSF-treated group showed significantly decreased myeloperoxidase activity and increased numbers of proliferating cell nuclear antigen (PCNA)-positive cells. Treatment with rhGM-CSF also affected expression of inflammatory cytokines in the ulcerative mucosal tissue. These results demonstrate the efficacy of plant-produced rhGM-CSF in wound healing and have significant implications for the development of rhGM-CSF as a therapeutic agent for ulcerative oral mucositis.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）是粒细胞和巨噬细胞谱系细胞成熟和功能的重要调节剂，在伤口愈合中也起着重要作用。在之前的研究中，我们在水稻细胞中表达了人 GM-CSF（水稻细胞源性人 GM-CSF；rhGM-CSF）。本研究旨在评估其对口腔黏膜炎愈合的影响。通过 5-氟尿嘧啶处理和机械划伤在叙利亚仓鼠颊囊中诱导口腔黏膜炎。从第 3 天到第 14 天，用 200 µL 生理盐水或含有 0.04、0.2 或 1 µg/mL rhGM-CSF 的相同体积溶液处理溃疡区域。与对照组相比，rhGM-CSF 处理的仓鼠的口腔黏膜溃疡面积减少。在愈合早期，rhGM-CSF 处理组的粘膜炎组织层中髓过氧化物酶活性显著降低，增殖细胞核抗原（PCNA）阳性细胞数量增加。rhGM-CSF 的治疗还影响溃疡性粘膜组织中炎症细胞因子的表达。这些结果表明植物源性 rhGM-CSF 在伤口愈合中的功效，并对开发 rhGM-CSF 作为治疗溃疡性口腔粘膜炎的治疗剂具有重要意义。
