An essential role of caspase 1 in the induction of murine lupus and its associated vascular damage.
An essential role of caspase 1 in the induction of murine lupus and its associated vascular damage.
复制标题
DOI：
10.1002/art.38225
复制
发表时间：
2014-01
影响因子：
13.3
通讯作者：
Kaplan, Mariana J.
中科院分区：
文献类型：
--
作者：
Kahlenberg, J. Michelle;Yalavarthi, Srilakshmi;Zhao, Wenpu;Hodgin, Jeffrey B.;Reed, Tamra J.;Tsuji, Noriko M.;Kaplan, Mariana J.
系统性红斑狼疮（SLE）是一种全身性自身免疫综合征，与器官损伤和心血管疾病（CVD）的风险升高有关，由先天性和适应性免疫途径激活引起。最近，SLE中炎性小体机制的激活增加已被描述。本研究采用降植烷狼疮模型，探讨炎症小体的中心酶caspase-1是否在SLE及其相关血管功能障碍的发展中发挥作用。将8周龄野生型或caspase-1 −/−小鼠通过腹膜内注射暴露于PBS或降植烷。注射后6个月，将小鼠安乐死，并评估狼疮表型和血管功能障碍的发展。虽然暴露于降植烷的野生型小鼠产生自身抗体和强烈的I型IFN应答，但缺乏半胱天冬酶-1的小鼠明显免受这些特征的影响，包括降植烷诱导的血管功能障碍。此外，免疫复合物肾小球肾炎的发展，在野生型小鼠中降植烷暴露后突出，在caspase-1 −/−小鼠中显着消除。这些结果表明，caspase-1是狼疮及其相关血管功能障碍发展的重要组成部分，并可能在环境暴露和自身免疫发展之间的相互作用中发挥重要作用，从而确定了一种新的治疗靶向途径。
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune syndrome associated with organ damage and an elevated risk of cardiovascular disease (CVD) resulting from activation of both innate and adaptive immune pathways. Recently, increased activation of the inflammasome machinery in SLE has been described. This study explores if caspase-1, the central enzyme of the inflammasome, plays a role in the development of SLE and its associated vascular dysfunction, using the pristane model of lupus. Eight-week old wild-type or caspase-1 −/− mice were exposed to PBS or pristane via intraperitoneal injection. Six months post injection, mice were euthanized and the development of a lupus phenotype and vascular dysfunction was assessed. While wild-type mice exposed to pristane develop autoantibodies and a strong type I IFN response, mice lacking caspase-1 are significantly protected from these features, including pristane-induced vascular dysfunction. Further, the development of immune-complex glomerulonephritis, prominent after pristane exposure in wild-type mice, is significantly abrogated in caspase-1 −/− mice. These results indicate that caspase-1 is an essential component in the development of lupus and its associated vascular dysfunction and may play an important role in the cross-talk between environmental exposures and autoimmunity development, thus identifying a novel pathway for therapeutic targeting.
登录
查看更多内容
影响因子：
5.5
作者：
Boxio, R;Bossenmeyer-Pourié, C;Nüsse, O
通讯作者：
Nüsse, O
影响因子：
4.4
作者：
Agrawal, Hemant;Jacob, Noam;Jacob, Chaim O.
通讯作者：
Jacob, Chaim O.
影响因子：
4.8
作者：
Green, Nathaniel M.;Moody, Krishna-Sulayman;Marshak-Rothstein, Ann
通讯作者：
Marshak-Rothstein, Ann
影响因子：
32.4
作者：
Jego, G;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
DOI：
10.4049/jimmunol.1001328
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lee PY;Kumagai Y;Xu Y;Li Y;Barker T;Liu C;Sobel ES;Takeuchi O;Akira S;Satoh M;Reeves WH
通讯作者：
Reeves WH