Redução da inflamação psoriásica em camundongos ∆dblGATA-1 ou tratados com EVASINA-4

Abstract

Psoriasis is a chronic inflammatory skin disease that affects 2-3% of the world's population. This disease has incomplete etiologic definition and is characterized by the unregulated proliferation and differentiation of keratinocytes, dermal angiogenesis and inflammatory infiltrate. Early changes in psoriasis are guided by the production of IL-23 by dendritic cells of the dermis that acts on Tγδ cells and promotes the release of IL-22 and IL-17. Together, these cytokines stimulate the production of IFN-γ and TNF that induce the proliferation of keratinocytes and the production of other cytokines, chemokines and adenosine monophosphate, factors that have important role in the amplification of the inflammatory response. The inflammatory infiltrate is composed mainly by neutrophils, but reports from the literature also describe the presence of eosinophiland their granules in the psoriasiform lesions and in the blood of patients with psoriasis. However, the role of eosinophils in psoriasis is not very well established. Objective: We aimed to investigate the role of eosinophils in Imiquimod (IMQ)-induced psoriasis inflammation in mice. Material and methods: Wild-type mice BALB/c and eosinophil deficient mice (∆dblGATA-1) were used. Experimental psoriasis was induced by topical application of IMQ on the back of animals for 4 consecutive days. In addition, a group of wild-type mice were treated with Evasin-4, a CCL11-binding protein, chemokine important for eosinophil recruitment. The analysis of inflammation and tissue damage were performed through clinical score, histological images, and enzymatic assays. Results: The topical use of IMQ on the back of wild-type animals induces an increase in eosinophil peroxidase activity in the lesion, which has intense scaling, erythema and neutrophil accumulation (myeloperoxidase activity), cells that are associated with psoriatic inflammation. ∆dblGATA-1 animals develop reduced skin lesions when compared to wild-type animals, as shown by lower clinical (scaling and erythema) and histopathological (acanthosis, parakeratosis and hyperkeratosis) scores and reduced inflammatory infiltrate. In addition, treatment with a Evasin-4 was effective in reducing the psoriasiform lesions in comparison to vehicle-treated group after IMQ application. Conclusion: In this study, we demonstrated that eosinophils have an important role in the development of cutaneous lesions in an experimental model of psoriasis. The absence or reduced presence of eosinophil is effective in reducing the clinical and inflammatory parameters of the psoriatic lesion, opening up new investigative possibilities, mainly in the deepening of the mechanisms involved in this context.