Phosphoinositide 3‑kinase δ/γ inhibition does not prevent concanavalin A‑induced hepatitis

Liu,Yuanyuan; Xiong,Li; Chang,Ying; Tang,Jianying; Ang,Wei; Yang,Tao; Pi,Weiyi; Yang,Xiaoyan; Ye,Weiwei; Luo,Youfu; Wang,Zhenling

doi:10.3892/mmr.2013.1649

November 2013 Volume 8 Issue 5

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November 2013 Volume 8 Issue 5

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Article

Phosphoinositide 3‑kinase δ/γ inhibition does not prevent concanavalin A‑induced hepatitis

Authors:
- Yuanyuan Liu
- Li Xiong
- Ying Chang
- Jianying Tang
- Wei Ang
- Tao Yang
- Weiyi Pi
- Xiaoyan Yang
- Weiwei Ye
- Youfu Luo
- Zhenling Wang
View Affiliations / Copyright

Affiliations: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, P.R. China
Pages: 1305-1310
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Published online on: August 22, 2013

https://doi.org/10.3892/mmr.2013.1649
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Abstract

An increasing number of studies have suggested that phosphoinositide 3‑kinase‑γ (PI3Kγ) and PI3Kδ are involved in the pathogenesis of autoimmune and inflammatory diseases, such as asthma and atherosclerosis. However, the underlying mechanism of acute hepatitis remains unknown. The present study aimed to determine the effect of PI3Kδ/γ inhibition on hepatic injury in a murine model of hepatitis induced by concanavalin A (ConA). It was demonstrated that the pharmacological inhibition of PI3Kδ/γ by TG100‑115 did not prevent liver damage following ConA challenge. Furthermore, the PI3Kδ/γ inhibition resulted in elevated transaminase activity in the serum, aggravated hepatic lesions characterized by hepatic necrosis, increased inflammatory cell infiltration and apoptosis of hepatocytes. Survival tests demonstrated that TG100‑115 significantly increased the death rate of mice following ConA challenge. In addition, TG100‑115 increased the serum levels of the proinflammatory cytokine IL‑2 following ConA injection. These results may oppose the development of PI3Kδ/γ inhibitors as therapeutic agents, particularly for the treatment of human hepatitis.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Phosphoinositide 3‑kinase δ/γ inhibition does not prevent concanavalin A‑induced hepatitis

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