RESUMEN
One of the most commonly observed adverse effects of cyclosporin A (CsA) is the development of gingival overgrowth (GO). Fibroblasts are involved in GO, but the question why only a percentage of patients undergoing CsA treatment shows this side-effect remains unanswered. In a previous study, CsA has been demonstrated to induce over-expression of phospholipase C (PLC) beta(1) in fibroblasts of patients with clinical GO, in cells from both enlarged and clinically healthy gingival sites. In this work, we assessed the expression of PLCbeta isoforms to investigate whether the exaggerated fibroblast response to CsA related to increased PLCbeta(1) expression could also be detected in CsA-treated patients without clinical signs of GO. Our results support the hypothesis of a multi-factorial origin of gingival overgrowth, including specific changes within the gingival tissues orchestrating fibroblastic hyper-responsiveness as a consequence of a long-term in vivo exposure to cyclosporin A.
Asunto(s)
Núcleo Celular/enzimología , Ciclosporina/efectos adversos , Fibroblastos/enzimología , Sobrecrecimiento Gingival/enzimología , Inmunosupresores/efectos adversos , Isoenzimas/biosíntesis , Fosfolipasas de Tipo C/biosíntesis , Adulto , Western Blotting , Estudios de Casos y Controles , Células Cultivadas , Inducción Enzimática , Fibroblastos/efectos de los fármacos , Predisposición Genética a la Enfermedad , Encía/efectos de los fármacos , Encía/enzimología , Sobrecrecimiento Gingival/inducido químicamente , Sobrecrecimiento Gingival/genética , Trasplante de Corazón , Humanos , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Fosfolipasa C beta , Estadísticas no ParamétricasRESUMEN
Inositol lipid cycle, among the pletora of signalling events, is directly involved in cell growth. It is located both in the cytoplasm and in the nucleus. Disturbances may cause uncontrolled proliferation of the cell and ultimately cancer. The phosphatidyl inositol phospolipase C (PLC) is a key enzyme in the hydrolysis of polyphosphoinositides (PIs) and could be differently involved in the normal and pathological cell growth. We report immunochemical and immunocytochemical demonstrations that the PLC isoforms are present in both cytoplasmic and nuclear compartments of low and fast proliferating hepatoma cells. The PLC activity is increased in fast proliferating cells, in which PLC delta1 and to a greater extent PLC delta4 are more expressed at cytosolic level, suggesting an involvement of PI specific PLCs in the progression of cell cycle and in the control of cell proliferation and possibly of neoplastic cell growth.
