Glucocorticoids inhibit the induction of nitric oxide synthase and the related cell damage in adenocarcinoma cells |
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Authors: | Kevin J. O Connor,Salvador Moncada |
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Affiliation: | Wellcome Research Laboratories, Langley Court, Beckenham, Kent, U.K. |
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Abstract: | Lipopolysaccharide (LPS) induced a time-dependent synthesis of nitric oxide (NO) in EMT6 adenocarcinoma cells, assayed by accumulation of NO-derived nitrite in the medium. The induction NO synthesis was inhibited in a concentration-dependent manner by the glucocorticoids dexamethasone (IC50 = 5 nM) and hydrocortisone (IC50 = 20 nM) and this effect was partially antagonized by progesterone and cortexolone. If addition of dexamethasone was delayed 6 h or more, inhibition of nitrite accumulation over 24 h was substantially reduced, indicating a lack of direct effect of glucocorticoids on the NO synthase. Nitrite accumulation was accompanied by cell damage, which was increased by L-arginine and inhibited by (L-NMMA) and dexamethasone. These data show that NO is a primary cytotoxic mediator and that suppression of its formation by glucocorticoids explains some of their anti-inflammatory and cytoprotective effects. |
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Keywords: | Glucocorticoid Nitric oxide synthase Adenocarcinoma cell Cell damage |
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