Expression of Interleukin-12 is Increased in Psoriatic Skin

Abstract

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.

In Vitro and In Situ Expression of IL-23 by Keratinocytes in Healthy Skin and Psoriasis Lesions: Enhanced Expression in Psoriatic Skin

“…1, nonstimulated keratinocytes from both normal and psoriatic lesional skin displayed mRNA for IL-23 p19 and IL-12/IL-23 p40, indicating that these cells constitutively express the two subunits of IL-23. In addition, we also demonstrated the constitutive presence of IL-12 p35 mRNA, confirming earlier studies (12,19,20).…”

An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis

“…It has been reported that IL-12 and IL-23 are up-regulated in psoriatic skin (30,36). These two cytokines are produced by APCs.…”

“…Produced by activated APCs (macrophages and DCs, including human epidermal Langerhans cells), IL-12 strongly promotes differentiation of naive T cells into IFN-␥-producing Th1 cells (25,(27)(28)(29). It has been reported that both IL-12p40 mRNA and IL-12p70 heterodimer are increased in psoriatic skin lesions (30). IL-23, a recently discovered member of the IL-12 family, is a disulfidebridged complex of a unique p19 subunit and the p40 subunit of IL-12 (26,31).…”

Up-regulation of corticotropin releasing hormone is associated with the downregulation of corticotropin releasing hormone binding protein and up-regulation of IL- 33 and IL-8 expression in psoriasis

“…The results of western blots confirmed the mRNA expression determined by quantitative RT-PCR. Furthermore, it is believed that cytokines could be possible therapeutic targets for the treatment of psoriasis [22].…”