Anti-inflammatory effects in the skin of thymosin-β4 splice-variants
Anti-inflammatory effects in the skin of thymosin-β4 splice-variants
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DOI：
10.1046/j.1365-2567.2003.01616.x
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发表时间：
2003-05-01
期刊：
影响因子：
6.4
通讯作者：
Tigelaar, RE
中科院分区：
文献类型：
--
作者：
Girardi, M;Sherling, MA;Tigelaar, RE
小鼠皮肤中T细胞受体γ δ（+）（V γ 5（+））树突状表皮T细胞（DETC）的上皮内淋巴细胞（IEL）网络下调皮肤炎症，尽管机制尚不清楚。胸腺素-β 4（Tbeta 4）通过基因表达的系列分析被鉴定为肠道IEL中的主要转录物，其编码普遍存在的肌动蛋白结合蛋白（UTbeta 4）和限制于淋巴组织的剪接变体（LTbeta 4），所述肌动蛋白结合蛋白（UTbeta 4）被证明具有抑制嗜中性粒细胞浸润的能力，所述剪接变体（LTbeta 4）具有未知生物活性。新鲜分离的Vgamma 5（+）DETC表达两种形式，而在体外细胞活化后，只有LT β 4优先上调。为了比较LT β 4和UT β 4在体内皮肤中的抗炎性质，使用三种不同的策略评估合成多肽的生物活性：通过足垫海藻-角叉菜胶注射的中性粒细胞浸润;对12-O-十四酰基佛波醇13-乙酸酯的刺激性接触性皮炎;和对2，4-二硝基氟苯的过敏性接触性皮炎。这些研究清楚地表明，LT β 4的抗炎活性比UTbeta 4更广泛，而且通常更强。因此，T β 4的淋巴特异性形式的激活响应性表达可能是DETC和可能的其他IEL下调局部炎症的一种机制。
The intraepithelial lymphocyte (IEL) network of T-cell receptor gammadelta(+) (Vgamma5(+) ) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-beta4 (Tbeta4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UTbeta4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LTbeta4) with unknown bioactivity. Freshly isolated Vgamma5(+) DETCs expressed both forms, while only LTbeta4 was preferentially up-regulated after cellular activation in vitro . To compare the anti-inflammatory properties of LTbeta4 and UTbeta4 in the skin in vivo , the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad lambda-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LTbeta4 were broader and most often stronger than those of UTbeta4. Thus, the activation-responsive expression of the lymph-specific form of Tbeta4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation.