College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, 030801, People's Republic of China.
School of Chemistry and Material Science, Shanxi Normal University, Taiyuan, Shanxi, 030031, People's Republic of China.
Arch Microbiol. 2024 May 7;206(6):249. doi: 10.1007/s00203-024-03971-z.
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.
大肠杆菌（E. coli）可引发严重的临床牛乳腺炎，给奶牛场造成巨大损失。巨噬细胞向不同状态极化是对病原体感染的反应。番茄红素是一种天然存在的烃类类胡萝卜素，通过控制巨噬细胞的 M1/M2 状态来缓解炎症。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。将巨噬细胞与番茄红素共同培养 24 小时，然后接种大肠杆菌 6 小时。结果发现，0.5μmol/L 番茄红素显著提高了巨噬细胞活力，显著降低了乳酸脱氢酶（LDH）水平，而 2 和 3μmol/L 番茄红素显著提高了 LDH 活性。番茄红素处理显著降低了大肠杆菌组中 LDH 释放、诱导型一氧化氮合酶（iNOS）、CD86、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和磷酸酶和张力蛋白同源物（PTEN）表达的增加。0.5μmol/L 番茄红素显著增加了大肠杆菌诱导的 CD206、精氨酸酶 I（ARG1）、吲哚胺 2,3-双加氧酶（IDO）、几丁质酶 3 样 3（YM1）、PI3K、AKT、p-AKT、雷帕霉素靶蛋白（mTOR）、p-mTOR、含 jumonji 结构域蛋白 3（JMJD3）和干扰素调节因子 4（IRF4）表达的下调。此外，白果醇 C17:1（一种特异性 PTEN 抑制剂）、740YPDGFR（一种特异性 PI3K 激活剂）、SC79（一种特异性 AKT 激活剂）或 CHPG 钠盐（一种特异性 NF-κB 激活剂）显著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 通路，增加了 M2 巨噬细胞，从而响应大肠杆菌感染。这些结果有助于揭示大肠杆菌引起的牛乳腺炎的发病机制，为乳腺炎的防治提供了新的角度。
