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Clinical and Developmental Immunology
Volume 2013, Article ID 476856, 12 pages
http://dx.doi.org/10.1155/2013/476856
Research Article

Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/− Mice

1Cardiovascular Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, China
2Rheumatism Department, Second Affiliated Hospital and Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000, China
3Cardiology Department, Second Affiliated Hospital of Fujian Medical University Zhongshan North Road 34, Quanzhou, Fujian 362000, China
4Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, China

Received 4 May 2013; Revised 8 July 2013; Accepted 15 July 2013

Academic Editor: T. Nakayama

Copyright © 2013 Jing-qin Ni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.