LOCAL REGULATION OF ADRENAL STEROIDOGENESIS: IS IL-1Β INVOLVED?

NATALIA SANTUCCI, ROCÍO STAMPONE, SILVINA VILLAR, SILVANA VIRGINIA SPINELLI, MARÍA LUISA BAY, OSCAR BOTTASSO

Mar del Plata

Congreso; Reunión SAIC-SAI-SAFIS. Mar del Plata 14 al 17 de noviembre 2018; 2018

Adrenal steroidogenesis and immune responses (IR) are mutuallyregulated through the production of specific molecules helping toorchestrate an optimal response. Under pathological conditions,the IR attempts to eliminate the noxious stimulus and repair thedamage whereas the endocrine response pursues to avoid anexcessive inflammation. As an infectious disease, Tuberculosis ischaracterized by a substantial secretion of inflammatory cytokineslike IL-1β, which is mainly produced by macrophages. While IL-1βmodulates the adrenal steroidogenesis at the central level, it is notclear whether it exerts a local effect on the adrenal gland. Severalstudies suggest that Nuclear Receptors NR4As are potential keyfactors in inflammation and metabolism, for instance in steroidogenesisby modulating steroidogenic enzyme expression. Our formerstudies in the human cell line NCI-H295R (derived from a carcinomaof adrenal cortex), revealed that treatment with IL-1β 1.25 pg/ml +Fk (Forskolin), 24 h, increased cortisol and DHEA production respectcultures stimulated with Fk or left untreated. Cells exposed ornot to Fk or IL-1β expressed type 1 and type 2 IL-1β receptors. Fktreatment increased IL-1R2 mRNA respect to IL-1R1 (p<0.05). Analysison the expression of steroidogenic enzymes and NR4As mRNAtogether with the microRNAs (miRNAs) profile, according to differenttreatments showed that Cyp17A1 mRNA was augmented in Fk+IL-1β (p<0.05). NR4A1 and 2 mRNA were also increased in Fk andIL-1β+Fk cultures (p<0.001 vs. basal, both cases; and p<0.01 respectIL-1β-stimulated cultures). IL-1β+Fk-stimulated cultures, displayedhigher NR4A2 mRNA levels than Fk counterparts (p<0.05).Two out of 10 analyzed miRNAs had a differential expression, beingMiRNAS 26a-5p and 484 augmented in IL-1β+Fk cultures. Four independentcultures with biological triplicates were analyzed. IL-1βinduced changes in hormonal secretion, receptor expression, andmodifications in the miRNA profile on NCI-H295R cells are likely tobe involved in the regulatory mechanisms underlying adrenal steroidogenesis.