ISSN: 2476-2024

Diagnostic Pathology: Open Access
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  • Research Article   
  • Diagnos Pathol Open,
  • DOI: 10.4172/2476-2024.8.S13.006

The Role of IL-17 Imbalance in Promoting the Pyroptosis in ImmuneMediated Liver Injury through STAT3-IFI16 Axis

Wenfang Xu1, Yanan Wang1, Changzhong Jin2, Weiyang Zhang1, Jiangnan Chen1, Xuefang Chen1, Junli Gao3,4, Junshun Gao3,4 and Hong Wang3,4*
1Department of Clinical Laboratory, Affiliated Hospital of Shaoxing University, Shaoxing City, PR China
2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou City, PR China
3Department of Clinical Laboratory, Hangzhou Cosmos Wisdom Mass Spectrometry Center of Zhejiang University Medical School, Hangzhou City, PR China
4Department of Clinical Laboratory, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou City, PR China
*Corresponding Author : Dr. Hong Wang, Department of Clinical Laboratory, Hangzhou Cosmos Wisdom Mass Spectrometry Center of Zhejiang University Medical School, Hangzhou City, PR China, Email: wh@cwmda.com

Received Date: Jul 13, 2023 / Accepted Date: Aug 07, 2023 / Published Date: Aug 14, 2023

Abstract

Autoimmune Hepatitis (AIH), characterized with excessive production of proinflammatory cytokines and progressive damage of hepatocytes, is an inflammatory disease of unclear pathogenesis. AIH affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with a distinct morphology associated with cell bursting and release of proinflammatory cytokines. A deeper understanding of the pathogenesis of AIH and its related pyroptosis will contribute to the development of novel therapy for AIH patients. We aimed to investigate the role of Interleukin 17 (IL-17) in immune-mediated liver injury caused by Concanavalin A-induced AIH based on integrated study using primary mouse hepatocytes and BALB/c mouse model. The levels of cytokines were measured by ELISA, and RT-qPCR was conducted to detect the mRNA expression of STAT3 and IFI16. The protein expression of STAT3 and IFI16 was measured by western blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate the liver histopathological changes of the mice under different treatments. The primary mouse hepatocytes modeling demonstrated that the levels of IFI16, IL-1b, IL-18, LDH and STAT3 were significantly increased in hepatocytes treated with IL-17, and further elevated followed by STAT3-Overexpressed (STAT3-OE) lentivirus treatment relative to the controls (p<0.01). Importantly, cell pyroptosis was observed in hepatocytes treated with IL-17, and severe cell damage was observed after STAT3-OE lentivirus treatment. In addition, a binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. In the BALB/c mouse modeling, glutathione transaminase activity was enhanced in ConA-induced AIH mice compared to that in control group (p<0.01). Aggravated liver damage in mice treated with STAT3-OE lentivirus was observed. However, liver damage was alleviated in mice treated with anti-IL-17 neutralizing antibody or STAT3-knockdown lentivirus. Hence, IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in the progression of AIH-related liver injury through STAT3-IFI16 axis. Therapeutic potential of targeting IL-17-STAT3-IFI16 pathway for AIH patients deserve to be further investigated.

Keywords: Autoimmune hepatitis; IL-17; Pyroptosis; IL-17-STAT3- IFI16 axis; Liver injury

Citation: Xu W, Wang Y, Jin C, Zhang W, Chen J, et al. (2023) The Role of IL-17 Imbalance in Promoting the Pyroptosis in Immune-Mediated Liver Injury through STAT3-IFI16 Axis. Diagnos Pathol Open S13:006. Doi: 10.4172/2476-2024.8.S13.006

Copyright: © 2023 Xu W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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