Yu Guang-Min, Kubota Hirokazu, Okita Miki, Maeda Teruo
Department of Bioresource Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan.
Setouchi Field Science Center, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan.
PLoS One. 2017 May 25;12(5):e0178525. doi: 10.1371/journal.pone.0178525. eCollection 2017.
Mastitis is the most prevalent disease in dairy cattle worldwide and not only causes huge economic losses in the dairy industry but also threatens public health. To evaluate the therapeutic potential of melatonin in mastitis, we examined the ability of melatonin to protect bovine mammary epithelial cells (bMECs) from the harmful effects of lipopolysaccharide (LPS). We found that melatonin inhibited the LPS-binding protein-CD14-TLR4 signaling pathway in bMECs, which had opposing effects on pro-inflammatory and anti-inflammatory mediators. Melatonin decreased LPS-induced expression of pro-inflammatory cytokines, chemokines, and positive acute-phase proteins (APPs), including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, granulocyte-monocyte colony-stimulating factor, chemokine CC motif ligand (CCL)2, CCL5, serum amyloid A, haptoglobin, C-reactive protein, ceruloplasmin, and α-1 antitrypsin, and increased expression of the anti-inflammatory cytokine IL-1Ra and the negative APP fibrinogen. In addition, melatonin increased dityrosine levels but suppressed nitrite levels by upregulating the expression of Nrf2 and heme oxygenase-1 in the Nrf2 antioxidant defense pathway. Finally, melatonin administration increased the viability of LPS-stimulated bMECs. These results suggest that melatonin protects bMECs from LPS-induced inflammatory and oxidant stress damage and provide evidence that melatonin might have therapeutic utility in mastitis.
乳腺炎是全球奶牛中最普遍的疾病，不仅给乳制品行业造成巨大经济损失，还威胁公众健康。为了评估褪黑素在乳腺炎中的治疗潜力，我们检测了褪黑素保护牛乳腺上皮细胞（bMECs）免受脂多糖（LPS）有害影响的能力。我们发现褪黑素抑制了bMECs中的LPS结合蛋白-CD14-TLR4信号通路，这对促炎和抗炎介质产生了相反的影响。褪黑素降低了LPS诱导的促炎细胞因子、趋化因子和阳性急性期蛋白（APPs）的表达，包括肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6、粒细胞-单核细胞集落刺激因子、趋化因子CC基序配体（CCL）2、CCL5、血清淀粉样蛋白A、触珠蛋白、C反应蛋白、铜蓝蛋白和α-1抗胰蛋白酶，并增加了抗炎细胞因子IL-1Ra和阴性APP纤维蛋白原的表达。此外，褪黑素通过上调Nrf2抗氧化防御途径中Nrf2和血红素加氧酶-1的表达来增加二酪氨酸水平，但抑制亚硝酸盐水平。最后，给予褪黑素提高了LPS刺激的bMECs的活力。这些结果表明，褪黑素可保护bMECs免受LPS诱导的炎症和氧化应激损伤，并提供了褪黑素可能对乳腺炎具有治疗作用的证据。
