Análise da expressão gênica in situ de mRNA para moléculas moduladoras da resposta imune e da inflamação na psoríase e em placa.

Abstract

Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia. The pathophysiology of the disease is characterized by the interaction between the innate and adaptive immune system, mediated by the inappropriate activation of T lymphocytes, which are associated with a complex network of cells and inflammatory mediators acting synergistically in the induction and maintenance of the inflammatory process. The exacerbated production of molecules involved in its pathogenesis induces hyperproliferation of keratinocytes, causing them to also produce some inflammatory factors and precursors of inflammation, potentially involved in the pathogenesis of psoriasis. In the face of this, the present study evaluated the in situ gene expression of mRNA of molecules that modulate the immune response and inflammation in plaque psoriasis. He also analyzed the gene expression of these molecules in patients with psoriasis on methotrexate therapy. The series consisted of 26 patients, of whom 21 were diagnosed with moderate to severe psoriasis (PASI> 10). Biopsies were collected from two different regions of the same patient, one directly from the lesional tissue and the other from non-lesional tissue. Of these, 15 were using methotrexate therapy and 6 were not using medication. As a control group, 5 healthy patients were selected. For in situ gene expression analysis, the material was processed for mRNA extraction, cDNA production, and finally qPCR of IL-17, IL-23, IL-22, IL-10, IFN-γ, TNF-α genes, TGF-βR2, ARG-1, ARG-2, iNOS, and GLUT-1. The results showed that the in situ gene expression of all evaluated genes was significantly higher in lesional and non-lesional tissue samples from patients with psoriasis than in tissue from healthy individuals. Expression of IL-17, IFN-γ, ARG-1 and ARG-2 genes was significantly higher in lesional tissue compared to non-lesional tissue. Methotrexate therapy increases IFN-γ, IL-10, TGF-βR2, and ARG-2 mRNA expression in patients with plaque psoriasis. The overexpression of these molecules in lesional and non-lesional tissue seems to act in the pathological state of epidermal hyperproliferation and the maintenance of the relevant inflammatory process in the immunopathogenesis of plaque psoriasis.