Impaired adrenal stress response in Toll-like receptor 2-deficient mice.
Septicemia is one of the major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. The family of Toll-like receptors (TLRs) is critical in the early immune response upon bacterial infection, and TLR polymorphisms are frequent in humans. Here, we demonstrate that TLR-2 deficiency in mice is associated with reduced plasma corticosterone levels and marked cellular alterations in adrenocortical tissue. TLR-2-deficient mice have an impaired adrenal corticosterone release after inflammatory stress induced by bacterial cell wall compounds. This defect appears to be mediated by a decrease in systemic and intraadrenal cytokine expression, including IL-1, tumor necrosis factor alpha, and IL-6. Our data demonstrate a link between the innate immune system and the endocrine stress response. The critical role of TLR-2 in adrenal glucocorticoid regulation needs to be considered in patients with inflammatory disease.
Bornstein
Stefan R
SR
Department of Medicine, Carl Gustav Carus University Hospital, University of Dresden, 01307 Dresden, Germany. stefan.bornstein@uniklinikum-dresden.de
Zacharowski
Paula
P
Schumann
Ralf R
RR
Barthel
Andreas
A
Tran
Nguyen
N
Papewalis
Claudia
C
Rettori
Valeria
V
McCann
Samuel M
SM
Schulze-Osthoff
Klaus
K
Scherbaum
Werner A
WA
Tarnow
Jörg
J
Zacharowski
Kai
K
D000302:Adrenal Cortex / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D019446:Endotoxemia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018805:Sepsis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013682:Teichoic Acids / Q000633:toxicity; D051195:Toll-Like Receptor 2
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone