Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies

Journal Article · Fri Jul 13 00:00:00 EDT 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.06.044· OSTI ID:22207945

Wang, Yuehai ^[1]; Huang, Ziyang ^[1]; Lu, Huixia ^[2]; Lin, Huili; Wang, Zhenhua ^[1]; Chen, Xiaoqing ^[3]; Ouyang, Qiufang ^[1]; Tang, Mengxiong; Hao, Panpan ^[2]; Ni, Jingqin ^[1]; Xu, Dongming ^[3]; Zhang, Mingxiang; Zhang, Qunye ^[2]; Lin, Ling ^[3]; others, and

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1. Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)
2. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China)
3. Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)

Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-} mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen tissue. The down-regulation of TLR4 signal molecules induced by LPS led to decreased expression of Bax and increased serum titers of ANA and anti-dsDNA antibody. Therefore, the TLR4 signal pathway may participate in maintaining the balance of splenocyte apoptosis and autoantibody production in ApoE{sup -/-} mice.

• OSTI ID: 22207945
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 423, Issue 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
ANTIBODIES
APOPTOSIS
ARTERIOSCLEROSIS
DNA
ENZYME IMMUNOASSAY
INTERFERON
KNOCK-OUT REACTIONS
LABELLING
MICE
PATHOGENESIS
PLANT TISSUES
RECEPTORS
SPLEEN
SPLENOMEGALY