4-1BB/4-1BBL interaction promotes obesity-induced adipose inflammation by triggering bidirectional inflammatory signaling in adipocytes/macrophages

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Obesity-induced adipose inflammation is characterized by recruitment of macrophages to adipose tissue and release of inflammatory cytokines. 4-1BB, a costimulatory receptor, modulates inflammatory processes through interaction with its ligand 4-1BBL on immune cell surfaces. In this study, we examined whether a 4-1BB/4-1BBL interaction between adipocytes and macrophages participates in obesity-induced adipose inflammation. We found that 4-1BB was expressed on adipocytes and was upregulated by obesity-related factors, which also enhanced 4-1BBL expression on macrophages. 4-1BB and/or 4-1BBL agonists, respectively, activated inflammatory signaling molecules (MAPK/IκBα and MAPK/Akt) in adipocytes and macrophages and enhanced the release of inflammatory cytokines (MCP-1, TNF-α, and IL-6). Moreover, disruption of the 4-1BB/4-1BBL interaction decreased the release of inflammatory cytokines from contact cocultured adipocytes/macrophages. These findings indicate that 4-1BB/4-1BBL-mediated bidirectional signaling in adipocytes/macrophages promotes adipose inflammation. 4-1BB and 4-1BBL may be useful targets for protection against obesity-induced adipose inflammation.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.