当前位置： SCI文献检索 > STEROIDS期刊下所有文献 > Interleukins 1α and 1β as regulators of steroidogenesis in human NCI-H295R adrenocortical cells.

Interleukins 1α and 1β as regulators of steroidogenesis in human NCI-H295R adrenocortical cells.

Abstract：

:Inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) regulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis at several levels. Although hypothalamic CRH secretion may be the primary mechanism by which these cytokines activate the HPA axis, IL-1 expression is increased within the adrenal glands in models for systemic inflammation, and IL-1 may augment adrenal glucocorticoid production. Our aim was to investigate the direct effects of IL-1α and IL-1β on adrenal steroidogenesis and expression of three key steroidogenic genes in human adrenocortical cells using the NCI-H295R cell line as a model. mRNAs encoding receptors for IL-1, TNF-α, and leukemia inhibitory factor (LIF) were detectable in the cell line (Affymetrix microarray analysis). Both IL-1α and IL-1β increased cortisol, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate production, and the accumulation of mRNAs for steroidogenic acute regulatory protein (STAR), 17α-hydroxylase/17,20-lyase (CYP17A1) and 3β-hydroxysteroid dehydrogenase 2 (HSD3B2) in these cells (P<0.05 for all). Both ILs augmented TNF-α- and LIF-induced STAR and CYP17A1 mRNA accumulation, and TNF-α-induced cortisol production (P<0.05 for all). Both ILs also increased the apoptotic index of the cells (P<0.05), which was efficiently neutralized by their specific antibodies. The IL-induced changes in the STAR, HSD3B2, and CYP17A1 protein levels were not as evident as those in the respective mRNA levels. In conclusion, the combined effect of inflammatory cytokines at the adrenal level in acute or chronic inflammatory states could significantly stimulate glucocorticoid production, and thus explain the observed discrepancy between the cortisol and ACTH concentrations sometimes seen in sepsis and chronic inflammatory states.

journal_name

Steroids

journal_title

Steroids

authors

Tkachenko IV,Jääskeläinen T,Jääskeläinen J,Palvimo JJ,Voutilainen R

doi

10.1016/j.steroids.2011.04.018

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

1103-15

issue

10-11

eissn

0039-128X

issn

1878-5867

pii

S0039-128X(11)00163-2

journal_volume

pub_type

杂志文章

在线工具

Interleukins 1α and 1β as regulators of steroidogenesis in human NCI-H295R adrenocortical cells.