Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury
Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury
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DOI：
10.1007/s13311-011-0084-7
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发表时间：
2012-01-01
影响因子：
5.7
通讯作者：
Riccardi, Carlo
中科院分区：
文献类型：
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作者：
Esposito, Emanuela;Bruscoli, Stefano;Riccardi, Carlo
脊髓损伤（SCI）是一种创伤性事件，其引起继发性和扩展性炎症，其特征在于免疫细胞（包括T淋巴细胞）的浸润、损伤部位中促炎介质的释放和组织变性。目前SCI的治疗方法仅限于糖皮质激素（GC），因为它们具有有效的抗炎活性。GC功效部分在于抑制NF-κ B、T淋巴细胞活化和随后的细胞因子产生的能力。在这项研究中，我们进行了实验，旨在测试的敏感性糖皮质激素诱导的亮氨酸拉链（GILZ）转基因（GILZ（TG））小鼠，其中GILZ是选择性过表达的T淋巴细胞，SCI诱导。与降低的炎症反应一致，与野生型同窝仔相比，GILZ（TG）对SCI的敏感性较低。值得注意的是，与野生型小鼠相比，GILZ（TG）明显抑制NF-κ B活化和核转位，减少T淋巴细胞活化和组织浸润，以及减少细胞因子释放。此外，GILZ（TG）显示肿瘤坏死因子-α，IL-1 β，诱导型一氧化氮合酶（iNOS）和酪氨酸的产生，细胞凋亡和神经组织损伤减少。总之，这些结果表明，GILZ模拟GC的抗炎作用，并代表了一个潜在的药理学目标，用于调节T淋巴细胞介导的免疫反应的炎症性疾病，如SCI。
Spinal cord injury (SCI) is a traumatic event that causes a secondary and extended inflammation characterized by infiltration of immune cells, including T lymphocytes, release of pro-inflammatory mediators in the lesion site, and tissue degeneration. Current therapeutic approaches for SCI are limited to glucocorticoids (GC) due to their potent anti-inflammatory activity. GC efficacy resides, in part, in the capability to inhibit NF-kappa B, T lymphocyte activation, and the consequent cytokine production. In this study, we performed experiments aimed to test the susceptibility of glucocorticoid-induced leucine zipper (GILZ) transgenic (GILZ(TG)) mice, in which GILZ is selectively over-expressed in T lymphocytes, to SCI induction. Consistent with a decreased inflammatory response, GILZ(TG) were less susceptible to SCI as compared to wild-type littermates. Notably, inhibition of NF-kappa B activation and nuclear translocation, diminished T lymphocytes activation and tissue infiltration, as well as decreased release of cytokines were evident in GILZ(TG) as compared to wild-type mice. Moreover, GILZ(TG) showed a reduced tumor necrosis factor-alpha, IL-1 beta, Inductible nitric oxide synthase (iNOS) and nytrotyrosine production, apoptosis, and neuronal tissue damage. Together these results indicate that GILZ mimics the anti-inflammatory effect of GC and represents a potential pharmacological target for modulation of T lymphocyte-mediated immune response in inflammatory disorders, such as SCI.