TNF-α regulates microglial activation via the NF-κB signaling pathway in systemic lupus erythematosus with depression

Abstract

This study aimed to investigate the effects of tumor necrosis factor-α (TNF-α) on systemic lupus erythematosus (SLE). The animal model of MRL/MpJ-Faslpr mice (MRL/lpr; lupus-prone mice) showed depression-like behaviors based on tail suspension, sucrose preference, and open field tests. Brain microglia were significantly activated with obvious increases in proinflammatory cytokines. In addition, in vitro experiments showed that TNF-α activated microglia by upregulating the NF-κB signaling pathway and proinflammatory cytokines. PDTC, a specific NF-κB inhibitor, effectively reduced TNF-α-mediated inflammatory signaling in microglia. These results suggest that TNF-α-induced microglial activation has a major role in neuroinflammation of SLE with depression.

Keywords: Microglia; Neuroinflammation; PDTC; Systemic lupus erythematosus; Tumor necrosis factor-α.