Lipopolysaccharide directly stimulates cortisol secretion by human adrenal cells by a cyclooxygenase-dependent mechanism.
Activation of the hypothalamo-pituitary-adrenal axis by bacterial lipopolysaccharide (LPS; endotoxin) is well documented, although there has been uncertainty about whether LPS exerts a direct effect at the level of the adrenal. The present study found that LPS caused a dose-dependent stimulation of basal cortisol secretion by the human adrenocortical cell line, NCI-H295R, without affecting aldosterone. The expression of both Toll-like receptor 2 (TLR2) and TLR4 was demonstrated in these cells, and the specific ligands for TLR4 (purified LPS and lipid A) and TLR2 (Pam3Cys) were found to stimulate cortisol release, suggesting that these receptors may mediate the effects of LPS in adrenal cells, as has been shown in other cell types. LPS was also found to stimulate prostaglandin E2 release by these cells. The effects of LPS on cortisol were attenuated in the presence of both indomethacin and a specific COX-2 inhibitor, but not a COX-1 inhibitor, suggesting an obligatory role for COX-2 activation and prostaglandin synthesis in the adrenal response to LPS.
Vakharia
K
K
Department of Endocrinology, William Harvey Research Institute, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, Suite 12, Dominion House, Bartholomew Close, London EC1A 7BE, United Kingdom.
Hinson
J P
JP
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000311:Adrenal Glands / Q000166:cytology*; D000450:Aldosterone / Q000378:metabolism; D002460:Cell Line; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008024:Ligands; D008050:Lipid A / Q000378:metabolism; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D008024:Ligands; D008050:Lipid A; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000450:Aldosterone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D006854:Hydrocortisone