Differential expression and action of Toll-like receptors in human adrenocortical cells.
During sepsis, an intact adrenal gland glucocorticoid stress response is critical for survival. Recently, we have shown that Toll-like receptors, particularly TLR2 and TLR4, are crucial in HPA axis regulation following inflammation, establishing a direct link between bacterial and viral ligands and the endocrine stress response. However, the exact role which TLRs play in adrenal homeostasis and malfunction is not yet sufficiently known. Using quantitative real-time PCR, confocal microscopy and the NF-kappaB reporter gene assay, we aimed to analyse both, expression and function of all relevant TLRs in the human adrenocortical cell line-NCI-H295R and adrenal cells in primary culture. Our results demonstrate a differential expression pattern of TLR1-9 in human adrenocortical cells as compared to immune cells and adrenocortical cancer cells. Consequently, activation of these cells by bacterial ligands leads to differential induction of cytokines including IL6, IL8 and TNF-alpha. Therefore, Toll-like receptors expression and function is a novel feature of the adrenal stress system contributing to adrenal tissue homeostasis, regeneration and tumorigenesis.
Kanczkowski
Waldemar
W
Department of Medicine, Carl Gustav Carus University Hospital, Technical University of Dresden, 01307 Dresden, Germany. Waldemar.kanczkowski@uniklinikum-dresden.de
Zacharowski
Kai
K
Wirth
Manfred P
MP
Ehrhart-Bornstein
Monika
M
Bornstein
Stefan R
SR
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; D016328:NF-kappa B; D020033:Protein Isoforms; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha