Toll-like receptor 9 expression in murine and human adrenal glands and possible implications during inflammation.

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.

• 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)

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

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)