Yawalkar N, Karlen S, Hunger R, Brand C U, Braathen L R
Dermatological Clinic and Institute of Immunology and Allergology, University of Bern, Inselspital, Switzerland.
J Invest Dermatol. 1998 Dec;111(6):1053-7. doi: 10.1046/j.1523-1747.1998.00446.x.
Although the precise underlying pathomechanisms of psoriasis have not been fully elucidated, previous reports suggest that T helper 1-type cytokines are critically involved in the pathogenesis of this disease. Interleukin-12 (IL-12), a heterodimeric cytokine, has been suggested to play a major role in the development of T helper 1 cell responses. In this study, the presence of IL-12 mRNA and protein was investigated in normal human skin as well as nonlesional and lesional psoriatic skin. Messenger RNA levels were determined in biopsy specimens by a standard and a nested reverse transcriptase-polymerase chain reaction method. Additionally, IL-12 protein expression was analyzed in situ by immunohistochemistry using an antibody recognizing IL-12 p70. Whereas specific transcripts for IL-12 p35 were reproducibly detected without any significant differences in all samples, enhanced IL-12 p40 mRNA signals were only found in lesional psoriatic skin as compared with normal and nonlesional psoriatic skin. Furthermore, immunoreactivity for IL-12 p70 was markedly increased in the psoriatic skin lesions and was predominantly expressed on mononuclear cells in the dermis. In conclusion, our data suggest a critical role for IL-12 in promoting and maintaining T cell activation and inducing T helper 1-type cytokines such as interferon-gamma in psoriasis. We speculate that IL-12 might be a key cytokine in the pathogenesis of psoriasis.
尽管银屑病确切的潜在发病机制尚未完全阐明,但既往报道提示辅助性T细胞1型细胞因子在该疾病的发病机制中起关键作用。白细胞介素-12(IL-12)是一种异二聚体细胞因子,被认为在辅助性T细胞1型反应的发展中起主要作用。在本研究中,对正常人皮肤以及银屑病非皮损和皮损皮肤中IL-12 mRNA和蛋白的存在情况进行了研究。通过标准和巢式逆转录聚合酶链反应方法测定活检标本中的信使RNA水平。此外,使用识别IL-12 p70的抗体通过免疫组织化学原位分析IL-12蛋白表达。虽然在所有样本中均可重复检测到IL-12 p35的特异性转录本,且无任何显著差异,但与正常和银屑病非皮损皮肤相比,仅在银屑病皮损皮肤中发现IL-12 p40 mRNA信号增强。此外,IL-12 p70的免疫反应性在银屑病皮损中明显增加,且主要在真皮中的单核细胞上表达。总之,我们的数据提示IL-12在银屑病中促进和维持T细胞活化以及诱导辅助性T细胞1型细胞因子如干扰素-γ方面起关键作用。我们推测IL-12可能是银屑病发病机制中的关键细胞因子。