Interleukin-17 activates and synergizes with the notch signaling pathway in the progression of pancreatic ductal adenocarcinoma

Wang, Xiaohong; Chen, Hao; Jiang, Rui; Hong, Xiafei; Peng, Junya; Chen, Wenyan; Jiang, Jialin; Li, Jie; Huang, Dan; Dai, Hongmei; Wang, Wenze; Lu, Junliang; Zhao, Yupei; Wu, Wenming

doi:10.1016/j.canlet.2021.03.003

Cited by 12 publications

(10 citation statements)

References 61 publications

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“…Social interaction in our study was found to be inversely correlated with the number of newly formed DCX + neurons in the dentate gyrus, and positively correlated with the NOTCH effector Hes1 gene expression (Figure 8). While IL-17A expression is known to be regulated by NOTCH signaling, it was recently reported that it can activate NOTCH signaling as well [51]. Similarly, in the murine schizophrenia model treated with mesenchymal stem cells, long term improvement in social behavior was also positively correlated with the NOTCH ligand Dll1 gene expression in the hippocampus [48].…”

Section: Discussionmentioning

confidence: 94%

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Willinger

Turgeman

2022

Cells

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Post-traumatic stress disorder (PTSD) is a psychiatric disorder accompanied by deficits in cognitive and social skills. Adult hippocampal neurogenesis is a lifelong phenomenon, with new neurons being formed in the granular cell layer of the dentate gyrus. Impaired neurogenesis is associated with multiple behavioral disorders including Alzheimer’s disease and schizophrenia. PTSD patients often present hippocampal atrophy and animal models clearly present impaired neurogenesis. Previous studies on PTSD patients demonstrated elevated levels of Th17 cells and plasma levels of the pro-inflammatory cytokine interleukin-17A (IL-17A). Since IL-17A can impair neurogenesis in mice, we thus hypothesized that decreasing the serum levels of IL-17A will increase hippocampal neurogenesis and alleviate symptoms in a murine model of PTSD. Surprisingly, our results showed that attempting to neutralize IL-17A with an antibody resulted in increased serum levels of IL-17A, while targeting IL-23, the upstream regulator of IL-17, did lower the levels of IL-17A in trauma-exposed mice. As expected, increased levels of serum IL-17A (in anti-IL-17A treated mice) resulted in impaired neurogenesis, reflected by reduced number of proliferating Ki67+ neural progenitors and newly formed DCX+ neurons, which was correlated with increased expression of HES1. Nevertheless, increased maturation was noted by the expression of SLIT2 and ACHE. In contrast, treatment with anti-IL-23 indeed resulted in increased neurogenesis. Behaviorally, both treatments did not affect trauma-related freezing behavior but did affect trauma-related social deficits. Unexpectedly, increased levels of serum IL-17A (in anti-IL-17A treated mice) prevented social deficits in trauma-exposed mice while anti-IL-23 exacerbated these deficits. We thus conclude that IL-17 is involved in regulating neurogenesis following exposure to stress but may be important in maintaining social behavior.

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Section: Discussionmentioning

confidence: 94%

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Willinger

Turgeman

2022

Cells

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“…Te DEGs in the two groups were mainly involved in the process of cancer-related signaling pathways and biological functions, including tumor microenvironment-related mechanisms and immunerelated mechanisms. Pancreatic cancer progression is associated with the tumor microenvironment, in which the expression of chemokines, accumulation of extracellular matrix, and the action of cancer-promoting cytokines accelerate the growth, invasion, and metastasis of pancreatic cancer [36][37][38]. IL-17 can promote the progression of pancreatic cancer, and the high expression of IL-17 can activate the Notch pathway through the NF-KB pathway.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Prognostic Model Based on Cuproptosis-Related lncRNA Signatures in Pancreatic Cancer

Jiang

Zhang

et al. 2022

Canadian Journal of Gastroenterology and Hepatology

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Aim. The aim of this study is to identify cuproptosis-related lncRNAs and construct a prognostic model for pancreatic cancer patients for clinical use. Methods. The expression profile of lncRNAs was downloaded from The Cancer Genome Atlas database, and cuproptosis-related lncRNAs were identified. The prognostic cuproptosis-related lncRNAs were obtained and used to establish and validate a prognostic risk score model in pancreatic cancer. Results. In total, 181 cuproptosis-related lncRNAs were obtained. The prognostic risk score model was constructed based on five lncRNAs (AC025257.1, TRAM2-AS1, AC091057.1, LINC01963, and MALAT1). Patients were assigned to two groups according to the median risk score. Kaplan–Meier survival curves showed that the difference in the prognosis between the high- and low-risk groups was statistically significant. Multivariate Cox analysis showed that our risk score was an independent risk factor for pancreatic cancer patients. Receiver operator characteristic curves revealed that the cuproptosis-related lncRNA model can effectively predict the prognosis of pancreatic cancer. The principal component analysis showed a difference between the high- and low-risk groups intuitively. Functional enrichment analysis showed that different genes were involved in cancer-related pathways in patients in the high- and low-risk groups. Conclusion. The risk model based on five prognostic cuproptosis-related lncRNAs can well predict the prognosis of pancreatic cancer patients. Cuproptosis-related lncRNAs could be potential biomarkers for pancreatic cancer diagnosis and treatment.

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“… 111 Cytokines are also key mediators in cancer, with IFN-γ contributing to the antitumor response 112 , 113 and IL-17 helping to promote tumors. 114 , 115 Based on cytokine secretion alone, it is difficult to predict whether MAIT cells play protective or pathogenic roles in the disease. Some in vitro experiments have shown that MAIT cells can directly kill tumor cells, yet definitive demonstration that this mechanism may operate in vivo is still lacking.…”

Section: Discussionmentioning

confidence: 99%

Mucosal-Associated Invariant T Cells in the Digestive System: Defender or Destroyer?

Zhang

Shen

Zhou

et al. 2023

Cellular and Molecular Gastroenterology and Hepatology

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Interleukin-17 activates and synergizes with the notch signaling pathway in the progression of pancreatic ductal adenocarcinoma

Cited by 12 publications

References 61 publications

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

Construction of a Prognostic Model Based on Cuproptosis-Related lncRNA Signatures in Pancreatic Cancer

Mucosal-Associated Invariant T Cells in the Digestive System: Defender or Destroyer?

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