JNK-1 deficiency limits macrophage-mediated antigen-induced arthritis.
JNK-1 deficiency limits macrophage-mediated antigen-induced arthritis.
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DOI：
10.1002/art.30271
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发表时间：
2011-06
影响因子：
--
通讯作者：
Corr, Maripat
中科院分区：
文献类型：
--
作者：
Guma, Monica;Ronacher, Lisa M.;Firestein, Gary S.;Karin, Michael;Corr, Maripat
阐明JNK1和JNK2在抗原诱导关节炎（AIA）中的非冗余作用。Jnk1或Jnk2基因被破坏的小鼠在完全的弗氏佐剂中注入甲基化的牛血清白蛋白（mBSA），然后在第21天在膝关节内注入mBSA。产生骨髓嵌合体并进行类似处理。取下关节并准备进行组织学评估。通过细胞因子和增殖反应验证T细胞反应，ELISA检测相对免疫球蛋白反应。采用qPCR检测细胞因子mRNA表达水平。研究了巯基乙酸酯和酶聚糖A诱导巨噬细胞在体内的募集和在体外的迁移。野生型（WT）小鼠关节内注射mBSA后4天开始每天注射肽抑制剂D-JNKi，并对炎症进行组织学评分。jnk1缺陷小鼠，而jnk2缺陷小鼠，炎症浸润和关节损伤减少。这种作用主要局限于造血细胞，但在注射mbsa的小鼠中保留了B细胞和T细胞的反应。jnk1缺失的巨噬细胞产生的细胞因子和趋化因子与WT对应的巨噬细胞相当。然而，在体内和体外，巨噬细胞的迁移受到损害。用肽抑制剂D-JNKi靶向JNK可显著减少WT小鼠的炎症和关节破坏。AIA依赖JNK1，但不依赖JNK2。JNK1是减少自身免疫性炎症的一个有希望的分子靶标，因为它的抑制作用会损害巨噬细胞的迁移。
To elucidate the non-redundant roles of JNK1 and JNK2 in antigen-induced arthritis (AIA). Mice that were genetically disrupted in Jnk1 or Jnk2 were primed with methylated BSA (mBSA) in complete Freund’s adjuvant and then given an intraarticular challenge with mBSA in the knee on day 21. Bone marrow chimeras were generated and similarly treated. Joints were harvested and prepared for histological assessment. T cell responses were verified by cytokine and proliferation responses, and relative immunoglobulin responses were measured by ELISA. Cytokine mRNA expression levels were measured by qPCR. Thioglycollate and zymosan A elicited macrophage recruitment was tested in vivo and migration was tested in vitro. The peptide inhibitor D-JNKi was injected daily starting four days after intraarticular mBSA injection in wild type (WT) mice and inflammation was histologically scored. JNK1-deficient, but not JNK2-deficient mice, had a reduction in inflammatory infiltration and joint damage. This effect was primarily restricted to hematopoetic cells, but B and T cell responses were preserved in mBSA-injected mice. JNK1-deficient macrophages produced cytokines and chemokines comparably to WT counterparts. However, macrophage migration was impaired in vivo and in vitro. Targeting JNK with the peptide inhibitor D-JNKi dramatically reduced inflammation and joint destruction in WT mice. AIA is dependent on JNK1, but not JNK2. JNK1 is a promising molecular target for reducing autoimmune inflammation as its inhibition impairs macrophage migration.
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影响因子：
--
作者：
Haringman, Jasper J.;Gerlag, Danielle M.;Tak, Paul P.
通讯作者：
Tak, Paul P.
影响因子：
27.4
作者：
Hammaker D;Firestein GS
通讯作者：
Firestein GS
影响因子：
9.2
作者：
Sabapathy, K;Hu, YL;Karin, M
通讯作者：
Karin, M
影响因子：
--
作者：
Guma, Monica;Ronacher, Lisa;Liu-Bryan, Ru;Takai, Shinji;Karin, Michael;Corr, Maripat
通讯作者：
Corr, Maripat
影响因子：
--
作者：
Han, ZN;Chang, LF;Firestein, GS
通讯作者：
Firestein, GS