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Study of Protein-protein Interactions in Autophagy Research
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The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in

Erica Buoso1, Marilisa Galasso1, Melania Ronfani1

  • 1Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia, Italy.

Toxicology and Applied Pharmacology
|April 17, 2017
PubMed

We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p'DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p'DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity and protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p'DDT and p,p'DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p'DDE exerting a stronger repressor effect than p,p'DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system.

Keywords:
Anabolic steroidsCytokinesEndocrine disrupting chemicalsHormonesImmune systemPesticidesSignal transduction

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