Local Regulation of Adrenal Steroidogenesis: Subtle in vitro Effects of IL-1β on the Human Cell Line NCI-H295R Steroid Production along with Changes in MicroRNA Profile and Orphan Nuclear Receptors NR4As

SANTUCCI, NATALIA; STAMPONE, ROCÍO; BRANDÃO FERREIRA DA SILVA, EDUARDO; VILLAR, SILVINA; SPINELLI, SILVANA; LINHARES-LACERDA, LEANDRA; RIBEIRO-ALVES, MARCELO; BAY, MARÍA LUISA; BOTTASSO, OSCAR

NEUROIMMUNOMODULATION.

KARGER

Año: 2020 vol. 27 p. 131 - 141

1021-7401

Introduction: IL-1β, a cytokine predominantly produced during the innate immune response, is well known for its pro-inflammatory effects and stimulating activity on the hypothalamus-pituitary-adrenal (HPA) axis. IL-1β stimulation of the HPA axis leads to the pituitary synthesis of adrenocorticotropin hormone followed by cortisol (and dehydroepiandrosterone - DHEA) release by the adrenal gland. While IL-1β modulates the adrenal steroidogenesis at the central level, it is unclear whether it also exerts an effect on the adrenal gland. Method: we studied the effect of IL-1β on adrenal steroid production and steroidogenic enzyme RNA expression in the human cell line NCI-H295R. We also explored eventual changes in the microRNAs (miRNAs) profile from IL-1β-treated NCI-H295R cells. Results: Transcripts encoding IL-1β receptors 1 and 2 were noticeable in the cell line, with cortisol and DHEA production increasing after cytokine treatment. The miRNAs profile was modified by IL-1β treatment to an extent which bears some relationship with the regulatory mechanisms underlying adrenal steroid production. Since orphan nuclear receptors NR4As have emerged as potential key factors for coordinating inflammatory and metabolic responses, cell expression studies were also carried out, to show a NR4As transcript augmentation following IL-1β treatment. Discussion/conclusions: The increased adrenal steroid production in response to IL-1β stimulation suggests an additional inflammatory/anti-inflammatory loop, which in addition to its physiological role might be implied in pathological states accompanied by an unbalanced immune-endocrine relationship.