Bukowska D, Kempisty B, Zawierucha P, Jopek K, Piotrowska H, Antosik P, Ciesiółka S, Woźna M, Brüssow K P, Jaśkowski J M
Institute of Veterinary Sciences, Poznan University of Life Sciences, Poznan, Poland.
Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland.
J Biol Regul Homeost Agents. 2014 Oct-Dec;28(4):637-48.
Pyometra, which is accompanied by bacterial contamination of the uterus, is defined as a complex disease associated with the activation of several systems, including the immune system. The objective of the study was to evaluate the gene expression profile in dogs with pyometra compared with those that were clinically normal. The study included uteri from 43 mongrel bitches (23 with pyometra, 20 clinically healthy). RNA used for the microarray study was pooled to four separated vials for control and pyometra. A total of 17,138 different transcripts were analyzed on the uteri of female dogs with pyometra and of healthy controls. From 264 inflammatory response-related transcripts, we found 23 transcripts that revealed a 10- to 77-fold increased expression. Thereby, the expression of interleukin 8 (IL8), interleukin-1-beta (IL1B), interleukin 18 receptor (IL18RAP), interleukin 1-alpha (IL1A), interleukin receptor antagonist (IL1RN) and interleukin 6 (IL6) increased 77-, 20-, 17-, 13-, 13- and 11-fold, respectively. Furthermore, the expression of the calcium binding proteins S100A8 was 44-fold higher, and that of S100A12 and S100A9 37-fold, respectively, in the uteri of canines with pyometra compared with that of the controls. Moreover, the expression of the transcripts of toll-like receptors (TLR8 and TLR2), integrin beta 2 (ITGB2), chemokine ligand 3 (CCL3), semaphorin 7A (SEMA7A), CD14 and prostaglandin-endoperoxide synthase 2 (PTGS2) was increased between 10- and 18-fold. Furthermore, after using RT-qPCR we found an increased expression of AOAH, IL1A, IL8, CCL3, IL1RN and SERPINE 1 mRNAs which can be served also as markers of the occurrence of pyometra in domestic bitches. In summary, it is concluded that up-regulation of interleukins may be used as a marker of the inflammatory response in dogs with pyometra. Moreover, all of the 23 up-regulated transcripts may be novel molecular markers of the pathogenesis of canine pyometra. Several proteins--products of these genes--may be recognized as potential biomarkers of this disease or as therapeutic targets in other mammalian species, including humans.
子宫蓄脓伴有子宫细菌污染，被定义为一种与包括免疫系统在内的多个系统激活相关的复杂疾病。本研究的目的是评估子宫蓄脓犬与临床正常犬相比的基因表达谱。该研究包括43只杂种母犬的子宫（23只患有子宫蓄脓，20只临床健康）。用于微阵列研究的RNA被汇集到四个单独的小瓶中，分别用于对照和子宫蓄脓样本。对患有子宫蓄脓的母犬和健康对照的子宫共分析了17,138种不同的转录本。在264种与炎症反应相关的转录本中，我们发现有23种转录本的表达增加了10至77倍。其中，白细胞介素8（IL8）、白细胞介素-1β（IL1B）、白细胞介素18受体（IL18RAP）、白细胞介素1-α（IL1A）、白细胞介素受体拮抗剂（IL1RN）和白细胞介素6（IL6）的表达分别增加了77倍、20倍、17倍、13倍、13倍和11倍。此外，与对照组相比，子宫蓄脓犬子宫中钙结合蛋白S100A8的表达高44倍，S100A12和S100A9的表达分别高37倍。此外，Toll样受体（TLR8和TLR2）、整合素β2（ITGB2）、趋化因子配体3（CCL3）、信号素7A（SEMA7A）、CD14和前列腺素内过氧化物合酶2（PTGS2）转录本的表达增加了10至18倍。此外，使用逆转录定量聚合酶链反应（RT-qPCR）后，我们发现AOAH、IL1A、IL8、CCL3、IL1RN和丝氨酸蛋白酶抑制剂1（SERPINE 1）mRNA的表达增加，这些也可作为家养母犬子宫蓄脓发生的标志物。总之，可以得出结论，白细胞介素的上调可作为子宫蓄脓犬炎症反应的标志物。此外，所有这23种上调的转录本可能是犬子宫蓄脓发病机制的新型分子标志物。这些基因的几种蛋白质产物可能被认为是这种疾病的潜在生物标志物或其他哺乳动物物种（包括人类）的治疗靶点。
