Zhang Xiaohua, Chen Yong, Yu Shuxia, Jin Bingjie, Liu Wenmin
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, 250021, Shandong Province, China.
Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, 250021, Shandong Province, China.
Inflammation. 2020 Dec;43(6):2128-2136. doi: 10.1007/s10753-020-01280-3.
Ulcerative colitis (UC) is a serious digestive system disease. Furthermore, the activation of C3a/C3aR axis promoted the expression of caspase-11. And higher levels of caspase-11 could induce the pyroptosis and inflammation of cells. However, some studies suggested that caspase-11 could promote and suppress the inflammation during the development of UC. In addition, whether C3a/C3aR axis could affect the development of UC by modulating the expression of caspase-11 is unclear. We established the UC rat model in this study. Next, the C3aR inhibitor was used to treat these rats at diverse stages of UC. Next, the HE staining was performed to detect the intestinal damage. ELISA was performed to reveal the expression of IL-6 and TNF-α in different stages of UC. Western blotting was used to detect the expression of caspase-11 and C3aR in different stages of UC. Stimulation of C3aR inhibitor in early stage of UC promoted the expression of C3aR and caspase-11 in later stage of UC. Treatment of C3aR inhibitor in later stage of UC inhibited the expression of C3aR and caspase-11 in later stage of UC. Furthermore, application of C3aR inhibitor in early stage of UC aggravates the damage of colon tissue and enhanced the secretion of TNF-α and IL-6 in the later stage of UC. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and suppressed the production of TNF-α and IL-6 in the later stage of UC. Application of C3aR inhibitor in early stage of UC induced the poor prognosis of UC by upregulating the expression of caspase-11. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and lead to the favorable prognosis of UC by inhibiting the expression of caspase-11.
溃疡性结肠炎（UC）是一种严重的消化系统疾病。此外，C3a/C3aR轴的激活促进了半胱天冬酶-11的表达。而较高水平的半胱天冬酶-11可诱导细胞焦亡和炎症。然而，一些研究表明，半胱天冬酶-11在UC发展过程中可促进和抑制炎症。此外，C3a/C3aR轴是否能通过调节半胱天冬酶-11的表达来影响UC的发展尚不清楚。在本研究中，我们建立了UC大鼠模型。接下来，使用C3aR抑制剂在UC的不同阶段对这些大鼠进行治疗。然后，进行苏木精-伊红（HE）染色以检测肠道损伤。采用酶联免疫吸附测定（ELISA）法揭示UC不同阶段白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达。利用蛋白质免疫印迹法检测UC不同阶段半胱天冬酶-11和C3aR的表达。在UC早期刺激C3aR抑制剂可促进UC后期C3aR和半胱天冬酶-11的表达。在UC后期用C3aR抑制剂治疗可抑制UC后期C3aR和半胱天冬酶-11的表达。此外，在UC早期应用C3aR抑制剂会加重结肠组织损伤，并增强UC后期TNF-α和IL-6的分泌。在UC后期用C3aR抑制剂治疗可缓解UC症状，并抑制UC后期TNF-α和IL-6的产生。在UC早期应用C3aR抑制剂通过上调半胱天冬酶-11的表达导致UC预后不良。在UC后期用C3aR抑制剂治疗可缓解UC症状，并通过抑制半胱天冬酶-11的表达导致UC预后良好。
