title: Effects of OX40-OX40L interaction on the nuclear factor of activated T cells c1 in ApoE-deficient mice.
abstract: We previously reported the emerging role of OX40-OX40L interaction in inflammation and atherosclerosis. However, the mechanism by which OX40-OX40L interaction contributes to pathogenesis is poorly understood. This study investigated the effects of OX40-OX40L interaction on the nuclear factor of activated T cells c1 (NFATc1) in ApoE(-/-) mice. Atherosclerotic plaque was induced via rapid perivascular carotid collar placement in ApoE(-/-) mice. The expression levels of OX40, OX40L, and NFATc1 in the lymphocytes were measured via real-time polymerase chain reaction and flow cytometry. The presence of NFATc1 in the atherosclerotic plaque was detected via immunohistochemistry, and the level of IL-4 was measured via enzyme-linked immunosorbent assay. The expression level of NFATc1 significantly increased in atherosclerotic lesion and in the leukocytes from the ApoE(-/-) mice. After stimulating OX40-OX40L interaction, the mRNA and protein expression levels of NFATc1 in the lymphocytes significantly increased. Meanwhile, anti-OX40LmAb significantly suppressed the expression of NFATc1 in the leukocytes and substantially elevated the level of IL-4. NFATc1 inhibitor markedly suppressed IL-4 production. This study suggests that OX40-OX40L interaction regulates the expression of NFATc1, which may play a critical role in atherosclerotic plaque formation, and may therefore have implications with pathophysiology of atherosclerosis.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, 212001, China, yanjinchuan@hotmail.com.
authors.forename: Jin-chuan
authors.initials: JC
authors.lastname: Yan
authors.forename: Liang-jie
authors.initials: LJ
authors.lastname: Xu
authors.forename: Cui-ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Zhong-qun
authors.initials: ZQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D053278:OX40 Ligand; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D053262:Receptors, OX40 / Q000096:biosynthesis / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D008562:Membrane Glycoproteins; D050778:NFATC Transcription Factors; D053278:OX40 Ligand; D012333:RNA, Messenger; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D015847:Interleukin-4
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