The OLR1/NF-κB feedback loop exacerbates HIV-1 Tat-induced microglial inflammatory response and neuronal apoptosis.

Abstract

Oxidized low density lipoprotein receptor 1 (OLR1), a type II integral membrane glycoprotein, is involved in multiple neurological diseases. However, the roles and mechanisms of OLR1 in HIV-associated neurocognitive disorder (HAND) remain unclear. In the central nervous system, Transactivator of transcription (Tat) induces inflammatory response in microglia, thereby leading to neuronal apoptosis. In the present study, we demonstrated that OLR1 expression was upregulated during ectopic expression of Tat or soluble Tat stimulus in BV-2 microglial cells. Moreover, OLR1 signaling was proved to facilitate Tat-triggered inflammatory response and alleviated the microglia-derived conditioned media-mediated HT-22 neural cells apoptosis in a NF-κB-dependent manner. Conversely, Tat augmented OLR1 expression via NF-κB signaling pathway. Finally, in mouse models, we determined that silencing of OLR1 significantly ameliorated Tat‑induced neuroinflammation and hippocampal neuronal death. Taken together, our study clarifies the potential role of the OLR1/NF-κB feedback loop in Tat-induced microglial inflammatory response and neuronal apoptosis, which could be a novel therapeutic target for relief of HAND.