title: 4-1BB/4-1BBL interaction promotes obesity-induced adipose inflammation by triggering bidirectional inflammatory signaling in adipocytes/macrophages.
abstract: 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.
authors: Department of Food Science and Nutrition, University of Ulsan, Ulsan, Republic of Korea.
authors: Thai Hien
authors: TH
authors: Tu
authors: Chu-Sook
authors: CS
authors: Kim
authors: Tsuyoshi
authors: T
authors: Goto
authors: Teruo
authors: T
authors: Kawada
authors: Byung-Sam
authors: BS
authors: Kim
authors: Rina
authors: R
authors: Yu
mesh_terms: D053330:4-1BB Ligand / Q000502:physiology*; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000209:etiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000502:physiology*
chemical_list: D053330:4-1BB Ligand; D016207:Cytokines; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9