Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice
To investigate the pathologic mechanisms of toll-like receptor 4 (TLR4) in lung injury and atherosclerosis, ApoE−/− or wild-type mice were intraperitoneally administered saline, lipopolysaccharides (LPS), or LPS plus TAK-242 (TLR4 inhibitor), respectively, twice a week for 4 weeks. Serum autoantibod...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2013/476856 |
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| author | Jing-qin Ni Qiufang Ouyang Ling Lin Ziyang Huang Huixia Lu Xiaoqing Chen Huili Lin Zhenhua Wang Dongming Xu Yun Zhang |
| author_facet | Jing-qin Ni Qiufang Ouyang Ling Lin Ziyang Huang Huixia Lu Xiaoqing Chen Huili Lin Zhenhua Wang Dongming Xu Yun Zhang |
| author_sort | Jing-qin Ni |
| collection | DOAJ |
| description | To investigate the pathologic mechanisms of toll-like receptor 4 (TLR4) in lung injury and atherosclerosis, ApoE−/− or wild-type mice were intraperitoneally administered saline, lipopolysaccharides (LPS), or LPS plus TAK-242 (TLR4 inhibitor), respectively, twice a week for 4 weeks. Serum autoantibody of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and cytokines of interferon-gamma (IFN-γ), tumor necrosis factor (TNF-α), and interleukin-1 (IL-1β) were assessed by ELISA. Hematoxylin and eosin (HE) and Perl's stains for lung pathomorphology as well as HE staining for atherosclerosis were employed. TLR4 in macrophages was detected by double immunofluorescent staining. While protein expressions of TLR4, nuclear factor-kappa B p65 (NF-κB p65), and B cell activating factor belonging to the TNF family (BAFF) were examined by immunohistochemistry. We found that serum autoantibody (ANA and anti-dsDNA), cytokines (IFN-γ, TNF-α, IL-1β), lung inflammation, and intima-media thickness in brachiocephalic artery were obviously increased after LPS challenge in both genotypes, but to a lesser extent in wild-type strains. And those alterations were alleviated by coadministration of LPS and TAK-242. Mechanistically, upregulation of TLR4, NF-κb, and BAFF was involved. We concluded that TLR4/NF-κb/BAFF in macrophages might be a possible common autoimmune pathway that caused lung injury and atherosclerosis. TLR4 signal will be a therapeutic target in atherosclerosis and immune-mediated lung injury. |
| format | Article |
| id | doaj-art-4ab4a271d4a249d099e4a4cd1d89a472 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-4ab4a271d4a249d099e4a4cd1d89a4722025-08-20T03:36:34ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/476856476856Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− MiceJing-qin Ni0Qiufang Ouyang1Ling Lin2Ziyang Huang3Huixia Lu4Xiaoqing Chen5Huili Lin6Zhenhua Wang7Dongming Xu8Yun Zhang9Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaCardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaRheumatism Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaCardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, ChinaRheumatism Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaCardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaCardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaRheumatism Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, ChinaKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, ChinaTo investigate the pathologic mechanisms of toll-like receptor 4 (TLR4) in lung injury and atherosclerosis, ApoE−/− or wild-type mice were intraperitoneally administered saline, lipopolysaccharides (LPS), or LPS plus TAK-242 (TLR4 inhibitor), respectively, twice a week for 4 weeks. Serum autoantibody of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and cytokines of interferon-gamma (IFN-γ), tumor necrosis factor (TNF-α), and interleukin-1 (IL-1β) were assessed by ELISA. Hematoxylin and eosin (HE) and Perl's stains for lung pathomorphology as well as HE staining for atherosclerosis were employed. TLR4 in macrophages was detected by double immunofluorescent staining. While protein expressions of TLR4, nuclear factor-kappa B p65 (NF-κB p65), and B cell activating factor belonging to the TNF family (BAFF) were examined by immunohistochemistry. We found that serum autoantibody (ANA and anti-dsDNA), cytokines (IFN-γ, TNF-α, IL-1β), lung inflammation, and intima-media thickness in brachiocephalic artery were obviously increased after LPS challenge in both genotypes, but to a lesser extent in wild-type strains. And those alterations were alleviated by coadministration of LPS and TAK-242. Mechanistically, upregulation of TLR4, NF-κb, and BAFF was involved. We concluded that TLR4/NF-κb/BAFF in macrophages might be a possible common autoimmune pathway that caused lung injury and atherosclerosis. TLR4 signal will be a therapeutic target in atherosclerosis and immune-mediated lung injury.http://dx.doi.org/10.1155/2013/476856 |
| spellingShingle | Jing-qin Ni Qiufang Ouyang Ling Lin Ziyang Huang Huixia Lu Xiaoqing Chen Huili Lin Zhenhua Wang Dongming Xu Yun Zhang Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice Clinical and Developmental Immunology |
| title | Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice |
| title_full | Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice |
| title_fullStr | Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice |
| title_full_unstemmed | Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice |
| title_short | Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice |
| title_sort | role of toll like receptor 4 on lupus lung injury and atherosclerosis in lps challenge apoe mice |
| url | http://dx.doi.org/10.1155/2013/476856 |
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