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Tuberculosis (Edinb) ; 96: 87-95, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26786659

RESUMEN

Mycobacterium tuberculosis (M. tb) is the etiological agent of pulmonary tuberculosis (TB); this disease remains a worldwide health problem. Yin-Yang-1 (YY1) plays a major role in the maintenance and progression of some pulmonary diseases, including pulmonary fibrosis. However, the role of YY1 in TB remains unknown. The aim of this study was to elucidate the role of YY1 in the regulation of CCL4 and its implication in TB. We determined whether YY1 regulates CCL4 using reporter plasmids, ChIP and siRNA assays. Immunohistochemistry and digital pathology were used to measure the expression of YY1 and CCL4 in a mouse model of TB. A retrospective comparison of patients with TB and control subjects was used to measure the expression of YY1 and CCL4 using tissue microarrays. Our results showed that YY1 regulates the transcription of CCL4; moreover, YY1, CCL4 and TGF-ß were overexpressed in the lung tissues of mice with TB during the late stages of the disease and the tissues of TB patients. The expression of CCL4 and TGF-ß correlated with YY1 expression. In conclusion, YY1 regulates CCL4 transcription; moreover, YY1 is overexpressed in experimental and human TB and is positively correlated with CCL4 and TGF-ß expression. Therefore, treatments that decrease YY1 expression may be a new therapeutic strategy against TB.


Asunto(s)
Quimiocina CCL4/metabolismo , Pulmón/microbiología , Tuberculosis Pulmonar/metabolismo , Factor de Transcripción YY1/metabolismo , Animales , Línea Celular , Quimiocina CCL4/genética , Inmunoprecipitación de Cromatina , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno , Humanos , Inmunohistoquímica , Pulmón/inmunología , Masculino , Ratones Endogámicos BALB C , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/patogenicidad , Interferencia de ARN , Estudios Retrospectivos , Transducción de Señal , Factores de Tiempo , Análisis de Matrices Tisulares , Transcripción Genética , Transfección , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Factor de Transcripción YY1/genética
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