Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice.
Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice.
复制标题
DOI：
10.1084/jem.20101457
复制
发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Lee DS
中科院分区：
文献类型：
--
作者：
Oh K;Park HB;Byoun OJ;Shin DM;Jeong EM;Kim YW;Kim YS;Melino G;Kim IG;Lee DS
在体外抑制转氨酶2减少博来霉素诱导的上皮细胞释放白细胞介素6，在体内减少肺部炎症和纤维化。肺纤维化是一种潜在的危及生命的疾病，可能由明显或无症状的炎症反应引起。然而，组织损伤转化为炎症和随后的纤维化的确切机制仍有待建立。在这里，我们表明，在肺损伤模型中，博莱霉素诱导上皮细胞分泌IL-6的转氨酶2（TG 2）依赖性的方式。这种反应代表了产生IL-17的T细胞分化和随后肺部炎症放大的关键步骤。上皮细胞，但不是炎性细胞，TG 2的重要作用在骨髓嵌合体中得到证实;与野生型小鼠相比，TG 2缺陷受体中的嵌合体显示炎症和纤维化减少，无论骨髓细胞表型如何。因此，上皮TG 2似乎是非感染性肺损伤后炎症的关键诱导物。我们进一步证明，成纤维细胞来源的TG 2，作用于转化生长因子-β的下游，在纤维发生的效应期也很重要。因此，TG 2代表了治疗干预的一个有趣的潜在靶点。
Inhibition of transglutaminase 2 reduces bleomycin-induced epithelial cell release of interleukin 6 in vitro and pulmonary inflammation and fibrosis in vivo. Pulmonary fibrosis is a potentially life-threatening disease that may be caused by overt or asymptomatic inflammatory responses. However, the precise mechanisms by which tissue injury is translated into inflammation and consequent fibrosis remain to be established. Here, we show that in a lung injury model, bleomycin induced the secretion of IL-6 by epithelial cells in a transglutaminase 2 (TG2)–dependent manner. This response represents a key step in the differentiation of IL-17–producing T cells and subsequent inflammatory amplification in the lung. The essential role of epithelial cells, but not inflammatory cells, TG2 was confirmed in bone marrow chimeras; chimeras made in TG2-deficient recipients showed reduced inflammation and fibrosis, compared with those in wild-type mice, regardless of the bone marrow cell phenotype. Epithelial TG2 thus appears to be a critical inducer of inflammation after noninfectious pulmonary injury. We further demonstrated that fibroblast-derived TG2, acting downstream of transforming growth factor-β, is also important in the effector phase of fibrogenesis. Therefore, TG2 represents an interesting potential target for therapeutic intervention.
登录
查看更多内容
DOI：
10.1161/01.atv.0000203503.82693.c1
发表时间：
2006-03-01
影响因子：
8.7
作者：
Boisvert, WA;Rose, DM;Terkeltaub, R
通讯作者：
Terkeltaub, R
DOI：
10.1164/ajrccm.158.2.9711075
发表时间：
1998-08-01
影响因子：
24.7
作者：
Jones, HA;Schofield, JB;Haslett, C
通讯作者：
Haslett, C
影响因子：
4.3
作者：
Kim, Robert;Meyer, Keith C
通讯作者：
Meyer, Keith C
DOI：
10.1165/ajrcmb.24.5.4064
发表时间：
2001-05-01
影响因子：
6.4
作者：
Chen, ES;Greenlee, BM;Moller, DR
通讯作者：
Moller, DR
影响因子：
1.7
作者：
Aujla, Shean J.;Dubin, Patricia J.;Kolls, Jay K.
通讯作者：
Kolls, Jay K.