HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response
Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE); however, the precise mechanism of HMGB1 in the pathogenic process of SLE...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/946748 |
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| _version_ | 1832555980988088320 |
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| author | Mudan Lu Shanshan Yu Wei Xu Bo Gao Sidong Xiong |
| author_facet | Mudan Lu Shanshan Yu Wei Xu Bo Gao Sidong Xiong |
| author_sort | Mudan Lu |
| collection | DOAJ |
| description | Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE); however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure. Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues. Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-α and IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response. Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE. |
| format | Article |
| id | doaj-art-39acb1e9aff9451ea6335c081f47586e |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-39acb1e9aff9451ea6335c081f47586e2025-02-03T05:46:35ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/946748946748HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory ResponseMudan Lu0Shanshan Yu1Wei Xu2Bo Gao3Sidong Xiong4Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaInstitute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaBackground/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE); however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure. Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues. Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-α and IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response. Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.http://dx.doi.org/10.1155/2015/946748 |
| spellingShingle | Mudan Lu Shanshan Yu Wei Xu Bo Gao Sidong Xiong HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response Journal of Immunology Research |
| title | HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response |
| title_full | HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response |
| title_fullStr | HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response |
| title_full_unstemmed | HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response |
| title_short | HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response |
| title_sort | hmgb1 promotes systemic lupus erythematosus by enhancing macrophage inflammatory response |
| url | http://dx.doi.org/10.1155/2015/946748 |
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