A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes.
A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes.
复制标题
DOI：
10.1084/jem.184.5.2007
复制
发表时间：
1996-11-01
期刊：
影响因子：
--
通讯作者：
Kolb-Bachofen V
中科院分区：
文献类型：
--
作者：
Bruch-Gerharz D;Fehsel K;Suschek C;Michel G;Ruzicka T;Kolb-Bachofen V
银屑病是一种常见的慢性皮肤病，由细胞免疫机制介导，其特征是表皮角质形成细胞大量中性粒细胞浸润和增殖激活。我们之前已经描述了诱导型一氧化氮合酶(INOS)在银屑病皮损的表皮角质形成细胞中的表达。在这项研究中，我们在银屑病皮肤活检组织和体外原代培养的人角质形成细胞中探讨了iNOS在银屑病炎症中的作用。用逆转录聚合酶链式反应检测了银屑病患者皮肤活检组织中iNOS酶的信使RNA(INOS MRNA)，而在特应性湿疹患者和健康志愿者的皮肤标本中未检测到iNOS基因。原位杂交和免疫组织化学显示，iNOS mRNA及其基因产物定位于银屑病皮损的表皮角质形成细胞。原位杂交进一步显示iNOS的mRNA表达与白介素8受体特异性的mRNA完全共存于基础生殖细胞层或正在进行的中性粒细胞炎症的基底层。由于银屑病角质形成细胞以前被证明表达IL-8的mRNA转录本，因此似乎有理由假设IL-8可以在自分泌环中诱导iNOS的表达。我们的体外实验证实了这一假设，实验表明，IL-8和干扰素联合诱导培养的人角质形成细胞中iNOS特异性mRNA和功能酶的表达。这些结果提示诱导型一氧化氮合酶与IL-8及其受体在银屑病皮损形成的早期起着重要作用。
Psoriasis is a common chronic skin disease mediated by cellular immune mechanisms and characterized by an intense neutrophil cell infiltrate and proliferative activation of epidermal keratinocytes. We have previously described the expression of the inducible nitric oxide synthase (iNOS) in epidermal keratinocytes of psoriatic skin lesions. In this study, the role of iNOS in psoriatic inflammation was explored ex vivo in psoriatic skin biopsies and in vitro in primary cultures of human keratinocytes. Messenger RNA for the iNOS enzyme (iNOS mRNA) was detected by reverse transcriptase polymerase chain reaction in skin biopsies from patients with psoriasis, but not in skin specimens from patients with atopic eczema or from healthy volunteers. As demonstrated by in situ hybridization and immunohistochemistry, expression of iNOS mRNA and its gene product was localized to the epidermal keratinocytes of psoriatic skin lesions. In situ hybridization further revealed a complete colocalization of mRNA expression for iNOS with interleukin (IL) 8 receptor-specific mRNA either in the basal germinative cell layer or at focal sites of ongoing neutrophil inflammation in suprabasal cell layers. Because psoriatic keratinocytes have previously been shown to express mRNA transcripts for IL-8, it seemed reasonable to hypothesize that iNOS expression could be induced in an autocrine loop by IL-8. This hypothesis was substantiated by our in vitro experiments showing that a combination of IL-8 and interferon gamma induces the expression of iNOS-specific mRNA and of the functional enzyme in cultured human keratinocytes. These results suggest an important role for iNOS in concert with IL-8 and its receptor early during the formation of psoriatic lesions.
登录
查看更多内容
DOI：
10.1084/jem.182.6.2097
发表时间：
1995-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Amin AR;Di Cesare PE;Vyas P;Attur M;Tzeng E;Billiar TR;Stuchin SA;Abramson SB
通讯作者：
Abramson SB
DOI：
10.1016/0167-5699(92)90118-q
发表时间：
1992-05-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
KOLB, H;KOLBBACHOFEN, V
通讯作者：
KOLBBACHOFEN, V
DOI：
10.1016/0167-5699(96)80599-8
发表时间：
1996-03-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
Michel, G;Kemeny, L;Ruzicka, T
通讯作者：
Ruzicka, T
影响因子：
6.5
作者：
GILLITZER, R;BERGER, R;STINGL, G
通讯作者：
STINGL, G
影响因子：
56.9
作者：
XIE, QW;CHO, HJ;NATHAN, C
通讯作者：
NATHAN, C