Co-culture of monocytes and zona fasciculata adrenal cells: An in vitro model to study the immune-adrenal cross-talk.
Animals
Cell Line, Tumor
Coculture Techniques
Dexamethasone
/ pharmacology
Gene Expression Regulation
/ drug effects
Humans
Immune System
/ metabolism
Interleukin-6
/ genetics
Lipopolysaccharides
/ pharmacology
Mice
Models, Biological
Monocytes
/ cytology
RNA, Messenger
/ genetics
Steroids
/ metabolism
THP-1 Cells
Time Factors
Zona Fasciculata
/ cytology
Adrenal cortex
Glucocorticoids
Inflammation
Steroidogenesis
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
15 04 2021
15 04 2021
Historique:
received:
13
10
2020
revised:
05
01
2021
accepted:
31
01
2021
pubmed:
12
2
2021
medline:
8
10
2021
entrez:
11
2
2021
Statut:
ppublish
Résumé
The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to re-establish homeostasis during periods of stress, including critical illness and major surgery. During critical illness, evidence suggests that locally induced inflammation of the adrenal gland could facilitate immune-adrenal cross-talk and, in turn, modulate cortisol secretion. It has been hypothesized that immune cells are necessary to mediate the effect of inflammatory stimuli on the steroidogenic pathway that has been observed in vivo. To test this hypothesis, we developed and characterized a trans-well co-culture model of THP1 (human monocytic cell)-derived macrophages and ATC7 murine zona fasciculata adrenocortical cells. We found that co-culture of ATC7 and THP1 cells results in a significant increase in the basal levels of IL-6 mRNA in ATC7 cells, and this effect was potentiated by treatment with LPS. Addition of LPS to co-cultures of ATC7 and THP1 significantly decreased the expression of key adrenal steroidogenic enzymes (including StAR and DAX-1), and this was also found in ATC7 cells treated with pro-inflammatory cytokines. Moreover, 24-h treatment with the synthetic glucocorticoid dexamethasone prevented the effects of LPS stimulation on IL-6, StAR and DAX-1 mRNA in ATC7 cells co-cultured with THP1 cells. Our data suggest that the expression of IL-6 and steroidogenic genes in response to LPS depends on the activation of intra-adrenal immune cells. Moreover, we also show that the effects of LPS can be modulated by glucocorticoids in a time- and dose-dependent manner with potential implications for clinical practice.
Identifiants
pubmed: 33571577
pii: S0303-7207(21)00039-3
doi: 10.1016/j.mce.2021.111195
pmc: PMC8024787
pii:
doi:
Substances chimiques
Interleukin-6
0
Lipopolysaccharides
0
RNA, Messenger
0
Steroids
0
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111195Subventions
Organisme : British Heart Foundation
ID : PG/14/72/31080
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/1992027/7163
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J008893/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
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