Role of PPARγ in the glucocorticoid-mediated effects on a macrophagic cell line stimulated with Mycobacterium tuberculosis

ARIANA DIAZ; LUCIANO D'ATILLIO; MARCELA MARCHESINI; NORA GOREN; BETTINA BONGIOVANNI; ÁGATA CEVEY; OSCAR BOTTASSO; ROCÍO DEL VALLE FERNÁNDEZ; FEDERICO PENAS; CLARA BATISTUTA; MARÍA L. BAY

Buenos Aires

Congreso; Reunión conjunta de Sociedades de Biociencias y 65ta Reunión de la SAI; Buenos Aires, 13-17 Noviembre 2017; 2017

Reunión Conjunta de Sociedades de Biociencia

Tuberculosis (TB) is a major health problem characterized by an immune-endocrine imbalance: high plasma levels of cortisol and pro- and anti-inflammatory mediators (IFN-g, IL-6, TGF-b and IL-10), with low levels of Dehydroepiandrosterone (DHEA). The etiologic agent, Mycobacterium tuberculosis (Mtb) is transmitted by air and captured by lung macrophages (MØ). MØ activation along with an efficient cellular immune response is required for Mtb elimination, which at the same time can mediate tissue damage. Glucocorticoids (GCs) are critical elements to counterbalance the immune-inflammatory reaction, with peroxisome proliferator-activated receptors (PPAR) being also implicated in this regard. The main forms of these receptors are: PPARα, PPARβδ and PPARγ. TB patients showed an increased expression of the PPARγ transcript in their peripheral blood mononuclear cells, which were positively associated with disease severity of the disease and cortisol plasma levels. Given this background, we now investigated whether PPARγ contributes to the inhibitory effect of GC on inflammatory MØs response (adherent human THP-1 cells) to Mtb (strain H37Rv killed by γ radiation -Mtbi-). Stimulated MØs (n=6-8 cultures) showed increased expression of mRNA PPARγ and IL-1 levels respect the unstimulated counterparts (p