Full-length IL-33 promotes inflammation but not Th2 response in vivo in an ST2-independent fashion.
Full-length IL-33 promotes inflammation but not Th2 response in vivo in an ST2-independent fashion.
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DOI：
10.4049/jimmunol.1200259
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发表时间：
2012-07-01
期刊：
影响因子：
--
通讯作者：
Atamas SP
中科院分区：
文献类型：
--
作者：
Luzina IG;Pickering EM;Kopach P;Kang PH;Lockatell V;Todd NW;Papadimitriou JC;McKenzie AN;Atamas SP
IL-33的表达在肺部疾病患者中升高，全长（未蛋白水解处理）IL-33是健康和疾病患者肺部的主要形式。为了确定IL-33的激活是否需要功能作用，我们比较了全长小鼠（flm）和成熟小鼠（mm） IL-33的体内活性。复制缺陷腺病毒构建体用于基因传递。这两种亚型均可引起淋巴细胞和中性粒细胞的肺浸润，而mil -33也可引起肺嗜酸性粒细胞增多和杯状细胞增生，并增加IL-4、IL-5、IL-13、IL-17、MCP-1和KC的表达。这种不同的影响与IL-33产生细胞的释放差异或IL-33亚型亚细胞分布的差异无关。细胞表面受体链ST2的种系缺失消除了mil -33诱导的th2相关效应（肺嗜酸性粒细胞增多、杯状细胞增生、IL-4和IL-5升高），但flmIL-33或mil -33诱导的淋巴细胞浸润并未因ST2缺失而完全消除。IL-33同种异构体的类似作用与基因表达的类似调节有关，特别是基质金属蛋白酶MMP3， MMP10和MMP13。因此，全长IL-33在体内以不依赖st2的方式发挥功能活性，其作用部分不同于成熟IL-33。这些异构体的不同作用，特别是成熟IL-33的亲th2作用，是由于IL-33受体链ST2的不同利用，而它们的相似作用是由于基因表达的调节。
Expression of IL-33 is elevated in patients with pulmonary diseases, and full-length (not proteolytically processed) IL-33 is the predominant form in the lungs in health and disease. To determine whether activation of IL-33 is needed for functional effects, activities of full-length mouse (flm) and mature mouse (mm) forms of IL-33 were compared in vivo. Replication-deficient adenoviral constructs were used for gene delivery. Both isoforms caused pulmonary infiltration of lymphocytes and neutrophils, whereas mmIL-33 also caused pulmonary eosinophilia and goblet cell hyperplasia, and increased expression of IL-4, IL-5, IL-13, IL-17, MCP-1, and KC. The different effects were not associated with differential release from IL-33-producing cells or by differences in subcellular distributions of IL-33 isoforms. Germline deficiency of the cell surface receptor chain ST2 abrogated the mmIL-33-induced Th2-associated effects (pulmonary eosinophilia, goblet cell hyperplasia, and increased IL-4 and IL-5), yet the lymphocytic infiltration induced by flmIL-33 or mmIL-33 was not fully abrogated by the absence of ST2. The similar effects of IL-33 isoforms were associated with comparable regulation of gene expression, notably matrix metalloproteinases MMP3, MMP10, and MMP13. Thus, full-length IL-33 is functionally active in vivo in an ST2-independent fashion, and its effects are partially different from those of mature IL-33. The different effects of these isoforms, particularly the pro-Th2 effects of mature IL-33, are due to differential utilization of the IL-33 receptor chain ST2, whereas their similar effects result from regulation of gene expression.
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影响因子：
--
作者：
Luzina, Irina G.;Todd, Nevins W.;Nacu, Natalia;Lockatell, Virginia;Choi, Jung;Hummers, Laura K.;Atamas, Sergei P.
通讯作者：
Atamas, Sergei P.
DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
DOI：
10.1016/j.bbrc.2009.12.107
发表时间：
2010-01-15
影响因子：
3.1
作者：
Ali, Shafaqat;Nguyen, Dang Quan;Martin, Michael Uwe
通讯作者：
Martin, Michael Uwe
影响因子：
--
作者：
Luzina, Irina G.;Papadimitriou, John C.;Atamas, Sergei P.
通讯作者：
Atamas, Sergei P.
DOI：
10.1084/jem.190.7.895
发表时间：
1999-10-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coyle AJ;Lloyd C;Tian J;Nguyen T;Erikkson C;Wang L;Ottoson P;Persson P;Delaney T;Lehar S;Lin S;Poisson L;Meisel C;Kamradt T;Bjerke T;Levinson D;Gutierrez-Ramos JC
通讯作者：
Gutierrez-Ramos JC