Neuroprotective Function of TNFAIP3 Interacting Protein 2 Against Oxygen and Glucose Deprivation/Reoxygenation-Induced Injury in Hippocampal Neuronal HT22 Cells Through Regulation of the TLR4/MyD88/NF-κB Pathway

Zhaoxian Yan; Yahui Chen; Xin Zhang; Lin Hua; Lifa Huang

doi:10.2147/NDT.S308360

Neuroprotective Function of TNFAIP3 Interacting Protein 2 Against Oxygen and Glucose Deprivation/Reoxygenation-Induced Injury in Hippocampal Neuronal HT22 Cells Through Regulation of the TLR4/MyD88/NF-κB Pathway

Neuropsychiatr Dis Treat. 2021 Jul 8:17:2219-2227. doi: 10.2147/NDT.S308360. eCollection 2021.

Authors

Zhaoxian Yan¹, Yahui Chen², Xin Zhang³, Lin Hua³, Lifa Huang³

Affiliations

¹ First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People's Republic of China.
² Department of Rheumatology, Ningbo No.6 Hospital, Ningbo, 315040, Zhejiang, People's Republic of China.
³ Department of Neurosurgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, People's Republic of China.

Abstract

Background: Tumor necrosis factor-α (TNF-α)-induced protein 3-interacting protein 2 (TNIP2) has been well demonstrated to act as a principal contributor to the development of inflammatory diseases; however, the role of TNIP2 in cerebral ischemic/reperfusion injury has never been studied.

Methods: Gene expression was examined by using quantitative real-time polymerase chain reaction and Western blot. The functional role of TNIP2 in oxygen and glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury was evaluated using cell counting kit-8, terminal deoxynucleotidyl transferase dutp nick end labeling assay and enzyme-linked immunosorbent assay. Commercial kits were applied to evaluate the activity of NF-kappa-B (NF-κB) and caspase-3, as well as the release of lactate dehydrogenase release (LDH).

Results: TNIP2 expression was substantially declined in HT22 cells following OGD/R stimulation. TNIP2 overexpression attenuated ODG/R-induced inflammation in HT22 cells, as evidenced by reduced levels of TNF-α, interleukin (IL)-1β, and intercellular cell adhesion molecule-1 (ICAM-1), and increased levels of IL-10. TNIP2 overexpression also reduced activity of NF-κB under ODG/R condition. Meanwhile, OGD/R treatment caused a reduction of cell viability and an elevation of cell apoptosis in HT22 cells, as indicated by the increase in LDH and caspase-3 activity. Whereas, OGD/R-induced HT22 cell injury was mitigated by TNIP2 overexpression in HT22 cells. Besides, we found the involvement of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/NF-κB pathway in the neuroprotective effect of TNIP2 on OGD/R-induced HT22 cell damage.

Conclusion: TNIP2 overexpression mitigates OGD/R-induced inflammatory response and apoptosis. Moreover, TLR4/MyD88/NF-κB pathway participates in the protective effect of TNIP2 on OGD/R-induced neuronal damage.

Keywords: TNF-α-induced protein 3-interacting protein 2; apoptosis; inflammation; ischemic reperfusion injury; toll-like receptor 4/myeloid differentiation factor 88/NF-kappa-B signaling.

Grants and funding

This study was funded by the Medical and Health Science and Technology Project of Zhejiang Province (grant No. 2017KY142).