A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes.

Abstract

SulTlmaryPsoriasis 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 mlLNA 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 ~/ 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.

NOS2 and CCL27: clinical implications for psoriasis and eczema diagnosis and management

“…NOS2 is absent in normal skin and significantly upregulated in psoriatic lesional skin compared with eczema where NOS2 was found to be expressed at lower levels or absent at both mRNA and protein level [10][11][12]. Along with this, NOS2 was found to be downregulated by Th2 cytokines and induced by Th1 cytokines as well as CXCL8, which is involved in angiogenesis and neutrophil recruitment [13,14].…”

Marek's Disease Virus (MDV) Encodes an Interleukin-8 Homolog (vIL-8): Characterization of the vIL-8 Protein and a vIL-8 Deletion Mutant MDV

“…9E3/CEF4, like IL-8, is greatly upregulated at sites of wounding (37) and appears to mitigate the healing cascade (36). Overproduction of IL-8 can be part of the host defense system but has been implicated also in inflammatory disorders, such as psoriasis (11) and rheumatoid arthritis (48). In some instances, IL-8-like chemokines, such as 9E3/CEF4, display strong angiogenic properties with a consequence of stimulating tumor cell growth (37) as well as stimulating growth of chick embyro fibroblasts (CEF) in culture (7).…”

Modelling Blood Flow Regulation by Nitric Oxide in Psoriatic Plaques

“…1) shows one clear qualitative difference, with a few measurements of particularly high NO release rates that are not reflected by the model. We hypothesize that these 'outliers' correspond to additional production of NO in suprabasal, as well as basal, epidermis; suprabasal keratinocytes have been found to express iNOS mRNA in a minority of psoriatic plaques (Bruch-Gerharz et al, 1996). Aside from this difference, there is good semi-quantitative comparison between the model and experiments.…”

“…Firstly, synthesis of NO, which occurs in cells in the basal layer of the epidermis; this has been established by staining tissue samples for the enzyme iNOS that causes the production (Kolb-Bachofen et al, 1994;Ormerod et al, 1998). This is not the only source of NO within a psoriatic plaque: NO is also produced in the dermal papillae and in some cases in the suprabasal epidermis (Bruch-Gerharz et al, 1996). However, we assume that the NO production in the basal epidermis is dominant, and occurs at a constant rate, a.…”