Rol de desmoglein-4 en la reacción inflamatoria cutánea en respuesta a imiquimod
Desmogleins (Dsgs) are cadherin-like glycoproteins present in the desmosomes, which are involved in adhesion, activation and cell migration processes. Dsgs are crucial for maintaining the structural integrity of several tissues, including skin. Keratinocytes (KC) are the predominant cells in the epi...
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| Autores principales: | , , , , , , , , , , , |
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| Publicado: |
2019
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| Acceso en línea: | https://bdigital.uncu.edu.ar/fichas.php?idobjeto=14392 |
| Sumario: | Desmogleins (Dsgs) are cadherin-like glycoproteins present in the desmosomes, which are involved in adhesion, activation and cell migration processes. Dsgs are crucial for maintaining the structural integrity of several tissues, including skin. Keratinocytes (KC) are the predominant cells in the epidermis, and among other functions, produce several inflammatory factors that modulate immune cells. Psoriasis (Ps) is a chronic cutaneous inflammatory disease that affects 2% of the world population. It is characterized by an unbalanced proliferation of KC, vascular thickening and inflammatory infiltration in dermis and epidermis. Our interest in evaluating the role of Dsg-4 in modulating the immune response during a cutaneous inflammatory process lies mainly in the fact that different Dsgs can modulate the activation of the KC. This process of cellular activation could be associated with changes in the phenotype and the production of immunomodulators, impacting the sensitivity to inflammatory reactions and pathological processes. Imiquimod (IMQ) is an immunomodulator that binds to the TLR-7 receptor and is used in rodents to induce lesions that resemble those seen in human Ps. The objective of our work is to evaluate the impact of Dsg-4 deficiency on leukocyte recruitment to skin in a rat Ps model induced by IMQ. For this purpose IMQ will be administered to Dsg-4 deficient rats and control Sprague-Dawley (SD) rats. Subsequently, skin biopsies will be obtained and then analyzed by flow cytometry (CD45 + and CD3 +); histopathological changes associated with the inflammatory process will be determined by conventional microscopy, and finally, mRNA levels of different inflammatory genes will be evaluated by real time PCR. With the development of this work, we hope to find evidence of an immunomodulatory role of Dsg-4, observing a severe leukocyte infiltration and higher expression of proinflammatory genes in Dsg-4 deficient rats, suggesting Dsg-4 influences dermatological processes mediated by the immune system as well the the progression of Ps-like disease. These results could have a potential impact on the design of possible diagnostic strategies for immune mediated skin diseases, in addition to contributing to understand the mechanism underlying the development of multifactorial skin diseases such as Ps. |
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