Staphylococcal-associated molecular patterns enhance expression of immune defense genes induced by IL-17 in mammary epithelial cells
Staphylococcal-associated molecular patterns enhance expression of immune defense genes induced by IL-17 in mammary epithelial cells
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DOI：
10.1016/j.cyto.2011.09.020
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发表时间：
2011-12-01
期刊：
影响因子：
3.8
通讯作者：
Rainard, Pascal
中科院分区：
文献类型：
--
作者：
Bougarn, Salim;Cunha, Patricia;Rainard, Pascal
白细胞介素- 17a （IL-17A）和IL-17F已被证明介导免疫系统和各种上皮组织之间的重要串扰，刺激对细菌感染的各种防御机制。许多研究表明，来自气道、肠和皮肤的上皮细胞对IL-17A和IL-17F的反应，但没有来自乳腺的反应。为了研究IL-17在乳腺免疫防御中的潜在作用，我们采用定量PCR和ELISA方法分析了重组牛IL-17A和IL-17F对原代牛乳腺上皮细胞（MEC）的影响。我们发现IL-17受体复合物的两个组成部分IL-17RA和IL-17RC在体外乳腺组织和MEC中表达（mRNA）。IL-17A增加了一些编码细胞因子、趋化因子和具有抗菌活性蛋白的基因的表达，IL-17F也增加了较小程度的表达，但反应的幅度不大。正如预期的那样，IL-17A或IL-17F与tnf - α的结合增强了反应。有趣的是，IL-17A与葡萄球菌脂壁酸或muramyl二肽（先天免疫系统的细菌激动剂）结合后，一些测试基因（如il - 8、CCL20、iNOS和CfB）的反应增强。这可以解释为表明IL-17A和IL-17F是专门为在化粪池环境中发挥其全部潜力而设计的。MEC反应的特征是趋化因子的表达不仅针对中性粒细胞（CXCL3和CXCL8），还针对单核白细胞（CCL2, CCL20）。IL-6的产生较低，炎症因子tnf - α和IL-1 β表达（mRNA），但蛋白不分泌。总之，我们的研究结果表明，IL-17A和IL-17F有可能调节乳腺对乳腺炎病原体的免疫反应。(C) 2011 Elsevier Ltd.版权所有。
Interleukin-17A (IL-17A) and IL-17F have been shown to mediate a crucial crosstalk between the immune system and various epithelial tissues, stimulating various defensive mechanisms to bacterial infections. A number of studies have characterized the response to IL-17A and IL-17F of epithelial cells from airways, intestine, and skin, but not from the mammary gland. To evaluate the potential contribution of IL-17 to the immune defense of the mammary gland, we analyzed the effects of recombinant bovine IL-17A and IL-17F on primary bovine mammary epithelial cells (MEC) by quantitative PCR and ELISA. We found expression (mRNA) of the two components of the IL-17 receptor complex, IL-17RA and IL-17RC, in mammary tissue and MEC in vitro. The expression of a number of genes encoding cytokines, chemokines and proteins endowed with antibacterial activities was increased by IL-17A, and to a lesser extent by IL-17F, but the magnitude of responses was modest. As expected, responses were augmented by the combination of IL-17A or IL-17F with TNF-alpha. Interestingly, responses of a few of the tested genes, such as IL8, CCL20, iNOS, and CfB, were augmented by the combination of IL-17A with staphylococcal lipoteichoic acid or muramyl dipeptide, bacterial agonists of the innate immune system. This can be interpreted as indicating that IL-17A and IL-17F are tailored to exert their full potential in a septic environment. MEC responses were characterized by the expression of chemokines targeting not only neutrophils (CXCL3 and CXCL8) but also mononuclear leucocytes (CCL2, CCL20). Production of IL-6 was low and the inflammatory cytokines TNF-alpha and IL-1 beta were expressed (mRNA) but proteins were not secreted. Altogether, our results suggest that IL-17A and IL-17F have a potential to modulate the mammary gland immune response to mastitis-causing pathogens. (C) 2011 Elsevier Ltd. All rights reserved.