Regulation of adrenal glucocorticoid synthesis by interleukin-10: a preponderance of IL-10 receptor in the adrenal zona fasciculata.
Several lines of evidence indicate that cytokines can affect adrenal function. To date most of these cytokines have been shown to be pro-inflammatory, such as interleukin (IL)-1, tumor necrosis factor (TNFalpha), and IL-6. However, we have previously shown that IL-10-/- (IL-10 knockout) mice have higher serum corticosterone levels than IL-10+/+ (wild type) mice following acute immune and physiologic stress, implying that IL-10, an anti-inflammatory cytokine, regulates glucocorticoid synthesis in a negative manner. Here, we show that IL-10 knockout mice produce more corticosterone under basal conditions as well (shown by ELISA). We further support this contention by showing that in Y-1 adrenocortical cells IL-10 inhibits steroid production (StAR) (measured by the production of the corticosterone precursor, progesterone), the expression of steroidogenic acute regulatory protein (semi-quantitative RT-PCR), as well as the activity of the proximal steroidogenic enzymes P450scc and/or 3beta-hydroxysteroid dehydrogenase (3beta-HSD) (measured by progesterone production in 22(R)-hydroxycholesterol-treated cells). Interestingly, all of the above-mentioned effects of IL-10 occur through its inhibition of ACTH effects, but not by IL-10 alone. Furthermore, immunocytochemistry data shows that the region of the adrenal gland responsible for the vast majority of corticosterone synthesis, the zona fasciculata, predominantly expresses the IL-10 receptor 1 (IL-10R1), with little expression in the zona glomerulosa and reticularis. These data demonstrate that IL-10 could play an important role in the regulation of glucocorticoid biosynthesis and in maintenance of homeostasis and immunity during periods of stress.
Koldzic-Zivanovic
Nina
N
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Tu
Huolin
H
Juelich
Terry L
TL
Rady
Peter L
PL
Tyring
Stephen K
SK
Hudnall
S David
SD
Smith
Eric M
EM
Hughes
Thomas K
TK
D015096:3-Hydroxysteroid Dehydrogenases / Q000276:immunology / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000276:immunology / Q000378:metabolism; D003345:Corticosterone / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D012313:RNA / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D015383:Zona Fasciculata / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000098682:Steroidogenic Acute Regulatory Protein; D016753:Interleukin-10; D012313:RNA; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003345:Corticosterone