Blockade of 4-1BB and 4-1BBL interaction reduces obesity-induced skeletal muscle inflammation

Ngoc Hoan Le, Chu Sook Kim, Thai Hien Tu, Hye Sun Choi, Byung Sam Kim, Teruo Kawada, Tsuyoshi Goto, Taesun Park, Jung Han Yoon Park, Rina Yu

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Obesity-induced skeletal muscle inflammation is characterized by increased macrophage infiltration and inflammatory cytokine production. In this study, we investigated whether 4-1BB, a member of the TNF receptor superfamily (TNFRSF9) that provides inflammatory signals, participates in obesity-induced skeletal muscle inflammation. Expression of the 4-1BB gene, accompanied by increased levels of inflammatory cytokines, was markedly upregulated in the skeletal muscle of obese mice fed a high-fat diet, in muscle cells treated with obesity factors, and in cocultured muscle cells/macrophages. In vitro stimulation of 4-1BB with agonistic antibody increased inflammatory cytokine levels in TNFα-pretreated muscle cells, and this effect was absent in cells derived from 4-1BB-deficient mice. Conversely, disruption of the interaction between 4-1BB and its ligand (4-1BBL) with blocking antibody decreased the release of inflammatory cytokines from cocultured muscle cells/macrophages. Moreover, deficiency of 4-1BB markedly reduced macrophage infiltration and inflammatory cytokine production in the skeletal muscle of mice fed a high-fat diet. These findings indicate that 4-1BB mediates the inflammatory responses in obese skeletal muscle by interacting with its ligand 4-1BBL on macrophages. Therefore, 4-1BB and 4-1BBL may be useful targets for prevention of obesity-induced inflammation in skeletal muscle.

Original languageEnglish
Article number865159
JournalMediators of Inflammation
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology


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