The colonic interleukin-19 aggravates the dextran sodium sulfate/stress-induced comorbidities due to colitis and anxiety
oleh: Qiongyu Li, Qiongyu Li, Qiongyu Li, Fantao Meng, Fantao Meng, Fantao Meng, Xiangxian Ma, Xiangxian Ma, Xiangxian Ma, Zhe Sun, Zhe Sun, Zhe Sun, Juanjuan Dai, Jing Liu, Jing Liu, Jing Liu, Dan Li, Peijia Cong, Peijia Cong, Peijia Cong, Ruixue Xu, Ruixue Xu, Ruixue Xu, Di Zhao, Di Zhao, Di Zhao, Wentao Wang, Wentao Wang, Wentao Wang, Dan Wang, Dan Wang, Dan Wang, Cuilan Liu, Cuilan Liu, Cuilan Liu, Faxiang Wang, Chen Li, Chen Li, Chen Li, Haifeng Lian, Haifeng Lian, Haifeng Lian
| Format: | Article |
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| Diterbitkan: | Frontiers Media S.A. 2023-03-01 |
Deskripsi
Comorbidities due to inflammatory bowel disease (IBD) and anxiety are commonly acknowledged; however, their underlying basis is unclear. In the current study, we first conducted a clinical retrospective analysis to identify the enhancive incidence rate of IBD before or after the epidemic of Corona Virus Disease 2019 (COVID-19), with higher Generalized Anxiety Disorder-7 (GAD-7), as well as poorer Gastrointestinal Quality of Life Index (GIQLI). Then, the dextran sodium sulfate (DSS) and chronic unpredictable stress (CUS)-induced IBD and anxiety comorbid models were established with the correlational relations between symptoms of IBD and anxiety-related behaviors. We found dysfunctional up-regulation of a new inflammatory factor interleukin (IL)-19 in the colon of DSS/CUS treated mice. Overexpression of IL-19 in colon induced anxious phenotypes, and accelerated the anxious condition and symptoms of colitis in the DSS/CUS model by promoting the expression of inducible nitric oxide synthase (iNOS), IL-1β, and IL-6 pro-inflammatory factors, and activating signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon. Furthermore, overexpression of IL-19 in the colon also reduced the expression levels of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), and cAMP-response element binding protein (CREB) signaling pathways activity in the hippocampus. These results suggest that IL-19 was a pivotal player in DSS/CUS-induced comorbidities of colitis and anxiety with different signaling pathways for the colon and hippocampus, which provides a candidate gene to explore the pathophysiology of comorbidities due to colitis and anxiety.