Bif‑1 inhibits activation of inflammasome through autophagy regulatory mechanism

Abstract

Inflammasome activation is a crucial mechanism in inflammatory responses. Bax-interacting factor 1 (Bif-1) is required for the normal formation of autophagosomes, but its ability to exert an inflammatory regulatory effect remains unclear. The aim of the present study was to explore the role of Bif-1 in inflammation, possibly mediated through autophagy regulation. Using a lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced inflammatory model in J774A.1 cells, the effect of Bif-1 on inflammasome activation and the underlying mechanisms involving autophagy regulation were investigated. Elevated levels of NLR family pyrin domain containing protein 3 inflammasome and interleukin-1β (IL-1β) proteins were observed in J774A.1 cells after LPS/ATP induction. Furthermore, Bif-1 and autophagy activity were significantly upregulated in inflammatory cells. Inhibition of autophagy resulted in inflammasome activation. Silencing Bif-1 expression significantly upregulated IL-1β levels and inhibited autophagy activity, suggesting a potential anti-inflammatory role of Bif-1 mediated by autophagy. Additionally, inhibition of the nuclear factor-κB (NF-κB) signaling pathway downregulated Bif-1 and inhibited autophagy activity, highlighting the importance of NF-κB in the regulation of Bif-1 and autophagy. In summary, the current study revealed that Bif-1 is a critical anti-inflammatory factor against inflammasome activation mediated by a mechanism of autophagy regulation, indicating its potential as a therapeutic target for inflammatory regulation.