Abstract：
High dietary intake of β-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by β-carotene-15,15\'-oxygenase (BCO1) and β-carotene-9\',10\'-oxygenase (BCO2) to produce retinol and apo-10\'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10\'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-β-apo-10\'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.
摘要：
高膳食摄入β-隐黄质(BCX，含氧维生素A类胡萝卜素）与吸烟者患肺部疾病的风险较低有关。BCX可被β-胡萝卜素-15,15'-加氧酶（BCO1）和β-胡萝卜素-9'裂解，10'-加氧酶（BCO2）产生视黄醇和apo-10'-类胡萝卜素。我们调查了BCX是否对香烟烟雾（CS）引起的肺损伤具有保护作用，依赖或不依赖BCO1/BCO2及其代谢物。BCO1-/-/BCO2-/-双敲除小鼠(DKO)和野生型(WT)同窝均补充BCX14天,然后暴露于CS另外14天。CS暴露显著诱导小鼠肺组织巨噬细胞和中性粒细胞浸润，不管基因型，与未暴露的同窝人相比。BCX治疗显著抑制CS诱导的炎症细胞浸润，支气管上皮增生，WT和DKO小鼠的肺泡气腔扩大，不管性别。BCX的保护作用与IL-6、TNF-α、和基质金属蛋白酶-2和-9。BCX治疗导致DKO小鼠肝脏BCX水平显着增加，但不是在WT小鼠中，肝视黄醇浓度显着增加。在任何组中都没有检测到apo-10'-类胡萝卜素。体外BCX，在相当剂量的3-OH-β-apo-10\'-胡萝卜素，在人支气管上皮细胞系中有效抑制脂多糖诱导的炎症反应。这些数据表明，在没有类胡萝卜素裂解酶的情况下，BCX可以作为CS诱导的肺部病变的有效保护剂。
