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Submitted on July 9, 2004
Accepted on November 19, 2004
Department of Endocrinology, William Harvey Research Institute, Barts and the London, Queen Mary's School of Medicine and Dentistry, QMUL, London, UK
* To whom correspondence should be addressed. E-mail: j.p.hinson{at}qmul.ac.uk.
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 (TLR) 2 and 4 was demonstrated in these cells and the specific ligands for TLR4 (purified LPS and Lipid A) and TLR 2 (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.
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