Yirong Ding1, Ji Zhang2, Rui Wang3. 1. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. 2. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 3. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: ruiwang@ecust.edu.cn.
Abstract
AIM: In view of the facts that tTG protein expression level and its enzyme activity increase in AD brains of both individuals and transgenic animals and compelling evidence of the involvement of inflammation in AD pathogenesis, tTG could be involved in the inflammation responses in the brain. In the present study, we examined the effects of the irreversible and the competitive inhibitor of tTG on the condition of lipopolysaccharide-induced mimic inflammation models in glial cells. METHODS: Western blot and tTG enzyme activity assay were applied to detect tTG and isopeptide protein levels and tTG enzyme activity. The production of nitric oxide and the expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were determined by Griess Reagents and Western blot respectively to assess anti-inflammatory effects. Moreover, the activation of AKT/mTOR signaling pathway was determined to evaluate the underlying mechanism of anti-inflammatory response. RESULTS: Irreversible and competitive inhibitor of tTG could ameliorate LPS-induced neuroinflammation in glial cells without cytotoxicity. Moreover, AKT/mTOR pathway may be involved in the anti-inflammatory response of tTG inhibitors. Therefore, NTU283 and Cystamine may alleviate inflammatory response in glial cells, probably through, at least partially, inhibiting the activation of AKT/mTOR signaling pathway. CONCLUSION: Our study provided some clues that tTG inhibitors NTU283 and Cystamine might be potential candidates for the treatments of neuroinflammation-related diseases, although more studies needed for further exploration.
AIM: In view of the facts that tTG protein expression level and its enzyme activity increase in AD brains of both individuals and transgenic animals and compelling evidence of the involvement of inflammation in AD pathogenesis, tTG could be involved in the inflammation responses in the brain. In the present study, we examined the effects of the irreversible and the competitive inhibitor of tTG on the condition of lipopolysaccharide-induced mimic inflammation models in glial cells. METHODS: Western blot and tTG enzyme activity assay were applied to detect tTG and isopeptide protein levels and tTG enzyme activity. The production of nitric oxide and the expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were determined by Griess Reagents and Western blot respectively to assess anti-inflammatory effects. Moreover, the activation of AKT/mTOR signaling pathway was determined to evaluate the underlying mechanism of anti-inflammatory response. RESULTS: Irreversible and competitive inhibitor of tTG could ameliorate LPS-induced neuroinflammation in glial cells without cytotoxicity. Moreover, AKT/mTOR pathway may be involved in the anti-inflammatory response of tTG inhibitors. Therefore, NTU283 and Cystamine may alleviate inflammatory response in glial cells, probably through, at least partially, inhibiting the activation of AKT/mTOR signaling pathway. CONCLUSION: Our study provided some clues that tTG inhibitors NTU283 and Cystamine might be potential candidates for the treatments of neuroinflammation-related diseases, although more studies needed for further exploration.
Authors: Kerui Fan; Ling Lin; Qing Ai; Jingyuan Wan; Jie Dai; Gang Liu; Li Tang; Yongqiang Yang; Pu Ge; Rong Jiang; Li Zhang Journal: Front Immunol Date: 2018-06-25 Impact factor: 7.561