Testosterone-Dependent Interaction between Androgen Receptor and Aryl Hydrocarbon Receptor Induces Liver Receptor Homolog 1 Expression in Rat Granulosa Cells

Androgens play a major role in the regulation of normal ovarian function; however, they are also involved in the development of ovarian pathologies. These contrasting effects may involve a differential response of granulosa cells to the androgens testosterone (T) and dihydrotestosterone (DHT). To determine the molecular pathways that mediate the distinct effects of T and DHT, we studied the expression of the liver receptor homolog 1 (LRH-1) gene, which is differentially regulated by these steroids. We found that although both T and DHT stimulate androgen receptor (AR) binding to the LRH-1 promoter, DHT prevents T-mediated stimulation of LRH-1 expression. T stimulated the expression of aryl hydrocarbon receptor (AHR) and its interaction with the AR. T also promoted the recruitment of the AR/AHR complex to the LRH-1 promoter. These effects were not mimicked by DHT. We also observed that the activation of extracellular regulated kinases by T is required for AR and AHR interaction. In summary, T, but not DHT, stimulates AHR expression and the interaction between AHR and AR, leading to the stimulation of LRH-1 expression. These findings could explain the distinct response of granulosa cells to T and DHT and provide a molecular mechanism by which DHT negatively affects ovarian function.     

Activation of Aryl Hydrocarbon Receptor (AhR) by Tranilast,an Anti-allergy Drug,Promotes miR-302 Expression and Cell Reprogramming

MiR-302 has been shown to regulate pluripotency genes and help somatic cell reprogramming. Thus, promotion of endogenous miR-302 expression could be a desirable way to facilitate cell reprogramming. By using a luciferase reporter system of the miR-302 promoter, we screened and found that an anti-allergy drug, tranilast, could significantly promote miR-302 expression. Further experiments revealed that two aryl hydrocarbon receptor (AhR) binding motifs on the miR-302 promoter are critical and that activation of AhR is required for tranilast-induced miR-302 expression. Consistently, not only tranilast but other AhR agonists promoted miR-302 expression. Furthermore, the activation of AhR facilitated cell reprogramming in a miR-302-dependent way. These results elucidate that miR-302 expression can be regulated by AhR and thus provide a strategy for promoting somatic cell reprogramming by AhR ligands.     

Staphylococcus epidermidis WF2R11 Suppresses PM2.5-Mediated Activation of the Aryl Hydrocarbon Receptor in HaCaT Keratinocytes

Probiotics and Antimicrobial Proteins - The skin supports a diverse microbiome whose imbalance is related to skin inflammation and diseases. Exposure to fine particulate matter (PM2.5), a major air...     

Differential Influences of the Aryl Hydrocarbon Receptor on Th17 Mediated Responses in vitro and in vivo

The aryl hydrocarbon receptor (AhR) has been attributed with anti-inflammatory effects in the development of pathological immune responses leading to experimental autoimmune encephalomyelitis (EAE) via the induction of regulatory T cells. In agreement with previously published findings, we find that TCDD administration confers protection from EAE, however, this immuno-modulatory effect was not the consequence of de novo Treg generation, but the inhibition of Th17 cell differentiation. Systemic application of FICZ at the time of immunization also reduced EAE pathology albeit to a lesser degree than TCDD. In vitro Th17 differentiation in the presence of AhR agonists, including TCDD, promoted IL-17 and IL-22 expression, but did not induce Treg differentiation. AhR affinity influenced the amounts of IL-17 and IL-22 protein that was secreted by Th17 cells, but did not seem to affect susceptibility to EAE in vivo. Making use of conditional AhR-deficient mice, we show that the anti-inflammatory effect of TCDD depends on AhR activation in both T cells and dendritic cells, further emphasising the ability of TCDD to interfere with T effector cell differentiation in vivo. The dichotomy between the in vivo and in vitro effects of AhR reveals the complexity of the AhR pathway, which has the capacity of affecting different AhR-expressing cell types involved in mounting immune responses, thus participating in defining their outcome.