Neuropsychiatric Disease and Treatment (Jul 2021)
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
Abstract
Zhaoxian Yan,1 Yahui Chen,2 Xin Zhang,3 Lin Hua,3 Lifa Huang3 1First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Department of Rheumatology, Ningbo No.6 Hospital, Ningbo, 315040, Zhejiang, People’s Republic of China; 3Department 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 ChinaCorrespondence: Lifa HuangDepartment of Neurosurgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Youdian Road, Shangcheng District, Hangzhou, 310006, Zhejiang, People’s Republic of ChinaEmail [email protected]: 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, ischemic reperfusion injury, inflammation, apoptosis, toll-like receptor 4/myeloid differentiation factor 88/NF-kappa-B signaling
