Siemieniuch Marta J, Szóstek Anna Z, Gajos Katarzyna, Kozdrowski Roland, Nowak Marcin, Okuda Kiyoshi
Dep. of Reproductive Immunology and Pathology, Polish Academy of Sciences, Olsztyn, Poland.
Graduate School of Environment and Life Science Okayama University, Okayama, Japan.
PLoS One. 2016 May 6;11(5):e0154934. doi: 10.1371/journal.pone.0154934. eCollection 2016.
Mares that fail to conceive or lose their embryos, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). In this study, the question was addressed: does SE fully activate selected mechanisms of innate immunity in mares? For this aim, expression of mRNAs for Toll-like Receptor 2 and 4 (TLR 2/4), interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF) was examined in control mares versus either mares suffering from chronic endometritis (ChE) or subacute suppurative endometritis (SSE). The concentrations of IL-1β, IL-6 and TNF-α in supernatants from endometrial tissue cultures after 4 h incubation were measured using the enzyme immunoassay (EIA) method. Eighty-two warmblood mares, of known breeding history, were enrolled in this study. Based on histopathological assessment, mares were classified as suffering from ChE, SSE or as being healthy. In addition, immuno-localization of both TLR2 and TLR4 as well as TNF-α was investigated in the equine endometria. The mRNA expression of TLR2 (P < 0.01), IL-1β (P < 0.0001), IL-6 (P < 0.0001) and TLR4 and TNF (P < 0.05) was up-regulated in endometria of mares suffering from SSE compared with unaffected mares. Concentrations of IL-6 and TNF-α were increased only in mares exhibiting SSE, compared with unaffected (P < 0.01 for both) and ChE mares (P < 0.05 for both). Immuno-localization of TNF-α and TLRs was confirmed, both in unaffected and SE-affected endometria, and was present in the luminal and glandular epithelia and stromal cells. The severity of inflammation impacts the immune response and fosters activation of innate immunity mechanisms, as observed in the endometria of mares. The intracellular localization of TLRs and TNF-α in the endometria indicates a key role of endometrial epithelial and stromal cells in the immune response and inflammation.
未能受孕或胚胎丢失且未表现出临床子宫内膜炎典型症状的母马，应怀疑患有亚临床子宫内膜炎（SE）。在本研究中，探讨了以下问题：SE是否能完全激活母马体内特定的固有免疫机制？为此，检测了对照母马与患有慢性子宫内膜炎（ChE）或亚急性化脓性子宫内膜炎（SSE）的母马中Toll样受体2和4（TLR 2/4）、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF）的mRNA表达。使用酶免疫分析（EIA）方法测定子宫内膜组织培养4小时后上清液中IL-1β、IL-6和TNF-α的浓度。本研究纳入了82匹有已知繁殖史的温血母马。根据组织病理学评估，将母马分为患有ChE、SSE或健康组。此外，还研究了TLR2和TLR4以及TNF-α在马子宫内膜中的免疫定位。与未受影响的母马相比，患有SSE的母马子宫内膜中TLR2（P < 0.01）、IL-1β（P < 0.0001）、IL-6（P < 0.0001）以及TLR4和TNF（P < 0.05）的mRNA表达上调。与未受影响的母马（两者均P < 0.01）和患有ChE的母马（两者均P < 0.05）相比，仅在患有SSE的母马中IL-6和TNF-α的浓度升高。在未受影响和受SE影响的子宫内膜中均证实了TNF-α和TLR的免疫定位，且存在于腔上皮、腺上皮和基质细胞中。如在母马子宫内膜中观察到的那样，炎症的严重程度影响免疫反应并促进固有免疫机制的激活。TLR和TNF-α在子宫内膜中的细胞内定位表明子宫内膜上皮细胞和基质细胞在免疫反应和炎症中起关键作用。
