title: Toll-like receptor 9 expression in murine and human adrenal glands and possible implications during inflammation.
abstract: 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.
authors.affiliation: Department of Anesthesia, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tran
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Berkels
authors.forename: Olaf
authors.initials: O
authors.lastname: Boehm
authors.forename: Paula A
authors.initials: PA
authors.lastname: Zacharowski
authors.forename: Georg
authors.initials: G
authors.lastname: Baumgarten
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.forename: Matthias
authors.initials: M
authors.lastname: Schott
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kanczkowski
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
mesh_terms: 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*
chemical_list: 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