First Author | Tran N | Year | 2007 |
Journal | J Clin Endocrinol Metab | Volume | 92 |
Issue | 7 | Pages | 2773-83 |
PubMed ID | 17473064 | Mgi Jnum | J:124389 |
Mgi Id | MGI:3721461 | Doi | 10.1210/jc.2006-2697 |
Citation | Tran N, et al. (2007) Toll-like receptor 9 expression in murine and human adrenal glands and possible implications during inflammation. J Clin Endocrinol Metab 92(7):2773-83 |
abstractText | 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. |