Toll-Like Receptor 9 Expression in Murine and Human Adrenal Glands and Possible Implications during Inflammation

N Tran, A Koch, R Berkels, O Boehm, PA Zacharowski, G Baumgarten, P Knuefermann, M Schott, W Kanczkowski, SR Bornstein, SL Lightman, KD Zacharowski

Research output: Contribution to journalArticle (Academic Journal)peer-review

25 Citations (Scopus)

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.
Translated title of the contributionToll-Like Receptor 9 Expression in Murine and Human Adrenal Glands and Possible Implications during Inflammation
Original languageEnglish
Pages (from-to)2773 - 2783
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume92 (7)
DOIs
Publication statusPublished - Jul 2007

Bibliographical note

Publisher: Endocrine Society

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