Yang Xiaowei, Zhu Jingjing, Tung Chun-Yu, Gardiner Gail, Wang Qun, Chang Hua-Chen, Zhou Baohua
Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, United States of America; Department of Veterinary Medicine, Southwest University at Rongchang, Rongchang, China.
Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, United States of America.
PLoS One. 2015 Feb 3;10(2):e0115330. doi: 10.1371/journal.pone.0115330. eCollection 2015.
Lunasin is a naturally occurring peptide isolated from soybeans and has been explored in cancer treatment. Lunasin inhibits NF-κB activation and thus pro-inflammatory cytokine and mediator production in macrophages. In this study we demonstrate that lunasin can effectively suppress allergic airway inflammation in two murine models of asthma. In an OVA+Alum sensitization model, intranasal lunasin treatment at the time of OVA challenges significantly reduced total cells counts in bronchoalveolar lavage (BAL) fluid and eosinophilia, peribronchiolar inflammatory infiltration, goblet cell metaplasia and airway IL-4 production. In an OVA+LPS intranasal sensitization model, lunasin treatment either at the time of sensitization or challenge has similar effects in suppress allergic airway inflammation including significantly reduced total cell and eosinophil counts in BAL fluid, inflammatory gene Fizz1 expression in the lung, and IL-4 production by OVA re-stimulated cells from mediastinal lymph nodes. We further show that intranasal instillation of OVA+lunasin significantly increases OVA-specific regulatory T cell (Treg) accumulation in the lung comparing to OVA only treatment. Taken together, our results suggest lunasin as an anti-inflammatory agent can be potentially used in asthma therapy or as an adjuvant to enhance the induction of antigen-specific Tregs and thus boost the efficacy of allergy immunotherapy.
芦那辛是一种从大豆中分离出的天然存在的肽,已在癌症治疗中进行了探索。芦那辛可抑制核因子-κB的激活,从而抑制巨噬细胞中促炎细胞因子和介质的产生。在本研究中,我们证明芦那辛能有效抑制两种小鼠哮喘模型中的过敏性气道炎症。在卵清蛋白+明矾致敏模型中,在卵清蛋白激发时进行鼻内芦那辛治疗可显著降低支气管肺泡灌洗(BAL)液中的总细胞计数和嗜酸性粒细胞增多、支气管周围炎性浸润、杯状细胞化生以及气道白细胞介素-4的产生。在卵清蛋白+脂多糖鼻内致敏模型中,在致敏或激发时进行芦那辛治疗对抑制过敏性气道炎症具有相似的效果,包括显著降低BAL液中的总细胞和嗜酸性粒细胞计数、肺中炎性基因Fizz1的表达以及卵清蛋白重新刺激的纵隔淋巴结细胞产生白细胞介素-4。我们进一步表明,与仅用卵清蛋白治疗相比,鼻内滴注卵清蛋白+芦那辛可显著增加肺中卵清蛋白特异性调节性T细胞(Treg)的积累。综上所述,我们的结果表明芦那辛作为一种抗炎剂可能潜在地用于哮喘治疗或作为佐剂以增强抗原特异性Treg的诱导,从而提高过敏免疫疗法的疗效。