A key role for Pre-B cell colony-enhancing factor in experimental hepatitis

Area of Science:

• Hepatology
• Immunology
• Biochemistry

Background:

• Pre-B cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase (NAMPT) or visfatin, is implicated in metabolic, inflammatory, and malignant diseases.
• Emerging evidence suggests that inhibiting PBEF's enzymatic activity may offer therapeutic benefits in acute experimental inflammation.

Purpose of the Study:

• To investigate the role of PBEF in human liver disease and experimental hepatitis models.
• To assess the therapeutic potential of PBEF inhibition in inflammatory liver conditions.

Main Methods:

• Serum PBEF levels and hepatic expression were analyzed in patients with chronic liver diseases.
• In vivo studies involved PBEF overexpression or FK866-mediated inhibition in concanavalin A (ConA) and D-galactosamine/lipopolysaccharide (LPS)-induced hepatitis models.
• In vitro experiments utilized PBEF-silenced mouse hepatocytes and primary murine Kupffer cells.

Main Results:

• Elevated PBEF serum levels and hepatic expression were observed in patients with chronic liver diseases.
• PBEF overexpression exacerbated ConA- and LPS-induced hepatitis, while FK866 treatment protected against ConA-induced liver injury and apoptosis.
• FK866 administration led to decreased hepatic nicotinamide adenine dinucleotide+ (NAD+) levels, reduced pro-inflammatory cytokine expression, and protected against LPS-induced hepatitis.
• In vitro, PBEF silencing diminished hepatocyte responses to inflammatory stimuli, and FK866 suppressed LPS-induced IL-6 production in Kupffer cells.

Conclusions:

• PBEF plays a significant role in the pathogenesis of experimental hepatitis.
• Targeted inhibition of PBEF represents a potential novel therapeutic strategy for managing inflammatory liver diseases.