Throughout the animal kingdom, steroid hormones have been implicated in the defense against microbial infection, but how these systemic signals control immunity is unclear. Here, we show that the steroid hormone ecdysone controls the expression of the pattern recognition receptor PGRP-LC in Drosophila, thereby tightly regulating innate immune recognition and defense against bacterial infection. We identify a group of steroid-regulated transcription factors as well as two GATA transcription factors that act as repressors and activators of the immune response and are required for the proper hormonal control of PGRP-LC expression. Together, our results demonstrate that Drosophila use complex mechanisms to modulate innate immune responses, and identify a transcriptional hierarchy that integrates steroid signalling and immunity in animals.
Peroxisome proliferator-activated receptor gamma (PPARg), a member of the nuclear receptor superfamily, is activated by several compounds, including the thiazolidinediones. In addition to being a therapeutic target for obesity, hypolipidaemia and diabetes, perturbation of PPARg signalling is now believed to be a strategy for treatment of several cancers, including breast. Although differential expression of PPARg is observed in tumours compared to normal tissues and PPARg agonists have been shown to inhibit tumour cell growth and survival, the interdependence of these observations is unclear. This study demonstrated that the potent, irreversible and selective PPARg antagonist GW9662 prevented activation of PPARg and inhibited growth of human mammary tumour cell lines. Controversially, GW9662 prevented rosiglitazone-mediated PPARg activation, but enhanced rather than reversed rosiglitazone-induced growth inhibition. As such, these data support the existence of PPARg-independent pathways and question the central belief that PPARg ligands mediate their anticancer effects via activation of PPARg.
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