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-alpha, and IL-1beta, -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.
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Authors | Nguyen Tran, Alexander Koch, Reinhard Berkels, Olaf Boehm, Paula A Zacharowski, Georg Baumgarten, Pascal Knuefermann, Matthias Schott, Waldemar Kanczkowski, Stefan R Bornstein, Stafford L Lightman, Kai Zacharowski |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 92
Issue 7
Pg. 2773-83
(Jul 2007)
ISSN: 0021-972X [Print] United States |
PMID | 17473064
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adjuvants, Immunologic
- CPG-oligonucleotide
- Cytokines
- NF-kappa B
- Oligodeoxyribonucleotides
- RNA, Messenger
- TLR9 protein, human
- Tlr9 protein, mouse
- Toll-Like Receptor 9
- Adrenocorticotropic Hormone
- Corticosterone
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Topics |
- Adjuvants, Immunologic
(pharmacology)
- Adrenal Cortex
(cytology, immunology, physiology)
- Adrenal Cortex Neoplasms
- Adrenocorticotropic Hormone
(blood)
- Animals
- Cell Line, Tumor
- Corticosterone
(blood)
- Cytokines
(blood)
- Gene Expression
(immunology)
- Humans
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- NF-kappa B
(metabolism)
- Oligodeoxyribonucleotides
(pharmacology)
- RNA, Messenger
(metabolism)
- Sepsis
(immunology, physiopathology)
- Toll-Like Receptor 9
(genetics, immunology)
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