Abstract：
Escherichia coli (E. coli) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections. Lycopene, a naturally occurring hydrocarbon carotenoid, relieved inflammation by controlling M1/M2 status of macrophages. Thus, we wanted to explore the effect of lycopene on polarization states of macrophages in E. coli-induced mastitis. Macrophages were cultivated with lycopene for 24, before E. coli inoculation for 6 h. Lycopene (0.5 μmol/L) significantly enhanced cell viabilities and significantly reduced lactic dehydrogenase (LDH) levels in macrophages, whereas 2 and 3 μmol/L lycopene significantly enhanced LDH activities. Lycopene treatment significantly reduced the increase in LDH release, iNOS, CD86, TNF-α, IL-1β and phosphatase and tensin homolog (PTEN) expressions in E. coli group. 0.5 μmol/L lycopene significantly increased E. coli-induced downregulation of CD206, arginase I (ARG1), indoleamine 2,3-dioxygenase (IDO), chitinase 3-like 3 (YM1), PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, jumonji domain-containing protein-3 (JMJD3) and interferon regulatory factor 4 (IRF4) levels. Moreover, Ginkgolic acid C17:1 (a specific PTEN inhibitor), 740YPDGFR (a specific PI3K activator), SC79 (a specific AKT activator) or CHPG sodium salt (a specific NF-κB activator) significantly decreased CD206, AGR1, IDO and YM1 expressions in lycopene and E. coli-treated macrophages. Therefore, lycopene increased M2 macrophages via inhibiting NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to E. coli infection in macrophages. These results contribute to revealing the pathogenesis of E. coli-caused bovine mastitis, providing the new angle of the prevention and management of mastitis.
摘要：
大肠杆菌(E.大肠杆菌)可诱发严重的临床牛乳腺炎，这是奶牛场遭受的巨大损失的罪魁祸首。巨噬细胞极化为各种状态是对病原体感染的反应。番茄红素,一种天然存在的碳氢化合物类胡萝卜素，通过控制巨噬细胞的M1/M2状态缓解炎症。因此，我们想探讨番茄红素对大肠杆菌诱导的乳腺炎中巨噬细胞极化状态的影响。在大肠杆菌接种6小时之前，用番茄红素培养巨噬细胞24。番茄红素（0.5μmol/L）显着增强了细胞活力，并显着降低了巨噬细胞中的乳酸脱氢酶（LDH）水平。而2和3μmol/L番茄红素显著增强LDH活性。番茄红素处理显著降低了LDH释放的增加，iNOS,CD86,TNF-α,IL-1β和磷酸酶和张力蛋白同源物(PTEN)在大肠杆菌组中的表达。0.5μmol/L番茄红素显着增加大肠杆菌诱导的CD206，精氨酸酶I（ARG1）的下调，吲哚胺2,3-双加氧酶（IDO），几丁质酶3样3（YM1），PI3K,AKT,p-AKT,哺乳动物雷帕霉素靶蛋白（mTOR），p-mTOR,含jumonji结构域的蛋白-3（JMJD3）和干扰素调节因子4（IRF4）水平。此外，银杏酸C17:1（一种特定的PTEN抑制剂），740YPDGFR（一种特定的PI3K激活剂），SC79（一种特定的AKT激活剂）或CHPG钠盐（一种特定的NF-κB激活剂）显着降低了番茄红素和大肠杆菌处理的巨噬细胞中CD206，AGR1，IDO和YM1的表达。因此,番茄红素通过抑制NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4途径增加M2巨噬细胞，以响应巨噬细胞中的大肠杆菌感染。这些结果有助于揭示大肠杆菌引起的牛乳腺炎的发病机理，为乳腺炎的预防和管理提供了新的角度。
