Inhibition of C3a/C3aR Axis in Diverse Stages of Ulcerative Colitis Affected the Prognosis of UC by Modulating the Pyrop
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ORIGINAL ARTICLE
Inhibition of C3a/C3aR Axis in Diverse Stages of Ulcerative Colitis Affected the Prognosis of UC by Modulating the Pyroptosis and Expression of Caspase-11 Xiaohua Zhang,1 Yong Chen,1 Shuxia Yu,1 Bingjie Jin,1 and Wenmin Liu
2,3
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 TNFα 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.
Abstract—
KEY WORDS: ulcerative colitis; C3a/C3aR axis; caspase-11; C3aR inhibitor; inflammation. 1
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, 250021, Shandong Province, China 2 Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, 250021, Shandong Province, China 3 To whom correspondence should be addressed at Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, 250021, Shandong Province, China. E-mail: [email protected]
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory bowel disease which could induce the inflammatory responses in diverse parts of the intestine. The ulcerative colitis often started with inflammation of the mucosa of the rectum and continuously induces inflammatory
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Zhang, Chen, Yu, Jin, and Liu responses at different locations of the intestinal mucos
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