Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation
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-induce...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/865159 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ngoc Hoan Le |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-504c82b2fedc4bcab44842437edf668a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-504c82b2fedc4bcab44842437edf668a2025-02-03T07:25:43ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/865159865159Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle InflammationNgoc Hoan Le0Chu-Sook Kim1Thai Hien Tu2Hye-Sun Choi3Byung-Sam Kim4Teruo Kawada5Tsuyoshi Goto6Taesun Park7Jung Han Yoon Park8Rina Yu9Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of KoreaDepartment of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of KoreaDepartment of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of KoreaDepartment of Biological Science, University of Ulsan, Ulsan 680-749, Republic of KoreaDepartment of Biological Science, University of Ulsan, Ulsan 680-749, Republic of KoreaGraduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, JapanGraduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, JapanDepartment of Food and Nutrition, Yonsei University, Seoul 120-749, Republic of KoreaDepartment of Food Science and Nutrition and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 200-702, Republic of KoreaDepartment of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of KoreaObesity-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.http://dx.doi.org/10.1155/2013/865159 |
| spellingShingle | 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 Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation Mediators of Inflammation |
| title | Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation |
| title_full | Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation |
| title_fullStr | Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation |
| title_full_unstemmed | Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation |
| title_short | Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation |
| title_sort | blockade of 4 1bb and 4 1bbl interaction reduces obesity induced skeletal muscle inflammation |
| url | http://dx.doi.org/10.1155/2013/865159 |
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