In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 92, No. 7 ( 2007-07-01), p. 2773-2783
Abstract:
Context: Sepsis is a leading cause of death in the Western world and can be associated with failure of the hypothalamic-pituitary-adrenal axis. A coordinated response of the adrenal and immune system is of vital importance for survival during sepsis. Within the immune response, Toll-like receptors (TLRs) play a crucial role by recognizing pathogen-associated molecules such as bacterial DNA. TLR-9 can detect motifs of unmethylated cytosine-phosphate-guanine (CpG) dinucleotides (CpG-DNA) being present in bacterial DNA. Objective: We investigated whether TLR-9 is expressed in human and murine adrenal glands and whether its activation is associated with an adrenal response. Design: Human fetal and adult adrenal glands; wild-type, C57BL/6 and TLR-9 deficient (TLR-9−/−) mice; and in vitro cell line models were used in the study. Setting: The study took place at a university hospital. Results: TLR-9 is expressed in human and murine adrenal glands, as well as in in vitro cell lines (Y-1 and NCI-H295R cells). CpG-oligodeoxynucleotide challenge caused a 3-fold increase in plasma levels of corticosterone in wild-type mice. This effect was not observed in TLR-9−/− mice. Furthermore, CpG-oligodeoxynucleotide challenge resulted in a strong release of several inflammatory cytokines, such as TNF-α, and IL-1β, -6, -10, and -12 in vivo as well as in vitro. Again, this effect was not present in TLR-9−/− mice. Conclusions: TLR-9 is present in both murine and human adrenal glands. TLR-9 stimulation led to a corticosterone and inflammatory cytokine response. TLR-9 may play a role in the regulation of the hypothalamic-pituitary-adrenal axis during conditions in which bacterial DNA is present.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jc.2006-2697
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2007
detail.hit.zdb_id:
2026217-6
