Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/−Mice
| Autor: | Dongming Xu, Huili Lin, Jingqin Ni, Huixia Lu, Ling Lin, Qiufang Ouyang, Yun Zhang, Ziyang Huang, Xiaoqing Chen, Zhenhua Wang |
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| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Proto-Oncogene Proteins B-raf lcsh:Immunologic diseases. Allergy Pathology medicine.medical_specialty Article Subject Immunology Hemorrhage Inflammation Lung injury Mice Apolipoproteins E medicine Animals Lupus Erythematosus Systemic Immunology and Allergy B-cell activating factor Autoantibodies Mice Knockout Toll-like receptor Systemic lupus erythematosus business.industry Macrophages NF-kappa B Autoantibody Lung Injury General Medicine Sinus of Valsalva Atherosclerosis medicine.disease Toll-Like Receptor 4 Disease Models Animal Antibodies Antinuclear TLR4 Cytokines Female lipids (amino acids peptides and proteins) Tumor necrosis factor alpha Inflammation Mediators medicine.symptom lcsh:RC581-607 business Research Article |
| Zdroj: | Clinical and Developmental Immunology, Vol 2013 (2013) Clinical and Developmental Immunology |
| ISSN: | 1740-2530 1740-2522 |
| DOI: | 10.1155/2013/476856 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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