Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis
Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis
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DOI：
10.1111/j.1365-2133.2011.10498.x
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发表时间：
2011-11-01
影响因子：
10.3
通讯作者：
Aiba, S.
中科院分区：
文献类型：
--
作者：
Fukushi, S.;Yamasaki, K.;Aiba, S.
结节性痒疹（PN）是一种慢性皮炎，以离散、凸起和坚固的丘疹结节为特征，伴有强烈的瘙痒。发病机制仍有待阐明。目的探讨Th1和Th2细胞因子在PN发病中的作用。方法通过检测细胞因子特征，如STAT1、STAT3和STAT6的磷酸化、HLA-DR和透明质酸的积累，揭示Th1和Th2细胞因子对PN病变表皮的影响。我们首先优化抗原检索方法，在银屑病、扁平苔藓和特应性皮炎活检标本的福尔马林固定石蜡切片上，用phospho-STAT1 （pSTAT1）、phospho-STAT3 （pSTAT3）、phospho-STAT6 （pSTAT6）、HLA-DR和透明质酸结合蛋白（HABP）抗体检测这些特征。在用干扰素- γ或白细胞介素(IL)-4/IL-13处理的皮肤等效模型中，进一步证实了Th1和Th2细胞因子对表皮中STAT1和STAT6的激活作用。我们采用相关免疫染色方法检测了22例PN的细胞因子特征。结果表明：(1)抗pstat6抗体全表皮染色19例，(2)抗pstat3抗体核染色21例，(3)HABP全表皮染色21例，(4)抗pstat1抗体分散染色8例，(5)HLA-DR膜表达阳性6例。结论与STAT6激活相关的Th2细胞因子以及激活STAT3的未知刺激在PN的发病机制中起主要作用。
Background Prurigo nodularis (PN) is a chronic dermatitis characterized by discrete, raised, and firm papulonodules with intense pruritus. The pathogenesis still remains to be elucidated.Objectives To clarify the role of Th1 and Th2 cytokines in the pathogenesis of PN.Methods We examined the cytokine signatures, such as phosphorylation of STAT1, STAT3 and STAT6, HLA-DR and hyaluronan accumulation, to reveal the Th1 and Th2 cytokine influence on the lesional epidermis of PN.Results We first optimized antigen retrieval methods to detect these signatures with antibodies for phospho-STAT1 (pSTAT1), phospho-STAT3 (pSTAT3), phospho-STAT6 (pSTAT6), HLA-DR and hyaluronic acid binding protein (HABP) on the formalin-fixed paraffin-embedded sections of psoriasis, lichen planus and atopic dermatitis biopsy samples. Activation of STAT1 and STAT6 in epidermis by Th1 and Th2 cytokines was further confirmed in a cultured skin equivalent model treated with interferon-gamma or interleukin (IL)-4/IL-13. With the relevant immunostaining methods, we examined the cytokine signatures in 22 cases of PN. The results revealed that (i) the entire epidermis of 19 cases was stained with anti-pSTAT6 antibody, (ii) 21 cases demonstrated nuclear staining with anti-pSTAT3 antibody, (iii) the entire epidermis of 21 cases was stained with HABP, (iv) the epidermis of eight cases showed scattered staining with anti-pSTAT1 antibody, and (v) six cases were positive for HLA-DR membrane expression.Conclusions These data indicated that Th2 cytokines related to STAT6 activation together with some unknown stimuli that activate STAT3 play a principal role in the pathogenesis of PN.