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


METHODS
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.


METHODS
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.
Tran
Nguyen
N
Department of Anesthesia, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom.
Koch
Alexander
A
Berkels
Reinhard
R
Boehm
Olaf
O
Zacharowski
Paula A
PA
Baumgarten
Georg
G
Knuefermann
Pascal
P
Schott
Matthias
M
Kanczkowski
Waldemar
W
Bornstein
Stefan R
SR
Lightman
Stafford L
SL
Zacharowski
Kai
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000302:Adrenal Cortex / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D000306:Adrenal Cortex Neoplasms; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D045744:Cell Line, Tumor; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000276:immunology / Q000503:physiopathology*; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone