Regulation of metabolic and transcriptional responses by the Thyroid Hormone in cellular models of murine macrophages

Although there is increasing evidence that the thyroid hormones could modulate macrophage functions, their global metabolic and transcriptional effects in cellular models of murine macrophages have not yet been examined. In this study we found that immortal macrophages, obtained by infection of mouse bone marrow cells with the J2 oncogene, are totally dependent on the thyroid hormone T3 for proliferation and survival. The hormone induces the activation of the main signaling pathways regulating cell growth and anabolic processes, altering the levels of key metabolites known to affect macrophage functions and modulating the expression of genes involved in stimulation of protein synthesis and cell proliferation, while reducing interferon-mediated signaling. The metabolic and transcriptomic effects of T3 in primary cultures of bone-marrow derived macrophages are much weaker than in the immortal cells, but the response to interferon is similarly reduced by the hormone. These results provide essential data on the pathways, metabolites and genes involved in the maintenance of immortal macrophages, as well as on the crosstalk between the cellular thyroid hormone status and the macrophage responses. Overall design: mRNA profiles of mouse primary bone marrow derived macrophages differentiated with L929 conditioned media (source M-CSF) treated or not with thyroid hormone T3, and compared with mouse bone marrow derived immortalized macrophages under the same treatment conditions