UPPER KERATINOCYTES OF PSORIATIC SKIN-LESIONS EXPRESS HIGH-LEVELS OF NAP-1/IL-8 MESSENGER-RNA INSITU

UPPER KERATINOCYTES OF PSORIATIC SKIN-LESIONS EXPRESS HIGH-LEVELS OF NAP-1/IL-8 MESSENGER-RNA INSITU
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DOI:
10.1111/1523-1747.ep12478128
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发表时间:
1991-07-01
影响因子:
6.5
通讯作者:
STINGL, G
STINGL, G
中科院分区:
医学1区
文献类型:
--
作者:
GILLITZER, R;BERGER, R;STINGL, G

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为了更好地了解调控银屑病(PS)疾病进展和活动的因素,我们研究了各种细胞因子在长期存在的PS皮损中的原位表达。与NAP-1/IL-8反义RNA探针的特异性杂交是角质形成细胞相关的,仅在皮损表皮的上层产生强而特异的信号,而在银屑病患者的正常皮肤或非银屑病患者的正常皮肤中不产生。有趣的是,NAP-1/IL-8转录本主要分布在细长乳突的尖端之间,呈点状聚集,但在下表皮区域和真皮间隔中缺失。我们一直未能在银屑病皮损中检测到相当数量的含有肿瘤坏死因子-α和/或白介素6-mRNA的细胞。这些结果支持这样的观点,即在PS中,IL-8而不是IL-6是重要的促病细胞因子。鉴于IL-8在体外和体内的已知作用,可以想象,这种物质在银屑病皮肤的主要病理变化中起着重要作用,即角质形成细胞过度增殖和白细胞浸润。在这种情况下,局部药物下调NAP-1/IL-8活性可能是PS的一种有前途的治疗策略。
In order to better understand the factors regulating disease promotion and activity in psoriasis (PS), we searched for the in situ expression of mRNA for various cytokines in long-standing PS skin lesions. Specific hybridization with a NAP-1/IL-8 anti-sense RNA probe was keratinocyte associated and yielded strong and specific signals exclusively in the upper layers of the lesional epidermis, but not in uninvolved skin from psoriatic patients or normal skin from non-psoriatics. Interestingly, NAP-1/IL-8 transcripts were focally clustered in a spotty pattern predominantly between the tips of elongated papillae, but were absent in the lower epidermal region and the dermal compartment. We consistently failed to detect appreciable numbers of TNF-alpha and/or IL-6 mRNA-containing cells in psoriatic lesions. These results support the notion that IL-8, rather than IL-6, is an important disease-promoting cytokine in PS. In view of the known in vitro and in vivo effects of IL-8, it is conceivable that this substance greatly contributes to the major pathologic changes seen in psoriatic skin, i.e., keratinocyte hyperproliferation and leucocyte infiltration. In this case, local pharmacologic down-regulation of NAP-1/IL-8 activity could be a promising therapeutic strategy in PS.