Corticosteroid-Induced Changes in Phospholipid Membranes as Mediators of Their Action*

Nelson, Don H.

doi:10.1210/edrv-1-2-180

Cited by 67 publications

(18 citation statements)

References 195 publications

(130 reference statements)

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“…The failure of hydrocortisone to prevent leukocyte infiltration and to reduce the pathological process despite the known capacity of glucocorticosteroids to diminish production of cytokines and arachidonic acid and to stabilize membranes (30,34) is consistent with the results reported by Meylan and Glauser (31). They reported a reduction in PMN migration very early (24 h) during the development of an acute exudative pyelonephritis treated with dexamethasone, but this effect vanished with the increasing inflammatory response, despite adequate dosage and schedule of administration.…”

Section: Discussionsupporting

confidence: 85%

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

Tardif

Beauchamp

Bergeron

et al. 1994

Antimicrob Agents Chemother

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In this study, the relationship between leukotrienes, peritubular cell infiltration with polymorphonuclear cells (PMNs) and renal tubular damage was investigated in a rat model of acute ascending pyelonephritis.Infection was induced by the injection of 105 CFU of Escherichia coli into the bladder and occlusion of the left ureter for 24 h. Treatment of infected animals was started 24 h after the induction of pyelonephritis with either hydrocortisone (25 mg/kg of body weight per day), the leukotriene inhibitor L-651,392 (10 mg/kg/day), or the vehicle of L-651,392 and was maintained for 5 days. At the end of treatment, the animals were killed, serum was collected, and both kidneys were removed for colony counts and histopathology. Renal function was evaluated by the measurement of blood urea nitrogen levels and creatinine clearance. The numbers of PMNs and mononuclear cells (MNs) in the cortex and medulla were recorded for all groups on plastic sections done from the left kidney. Infection alone (vehicle of L-651,392) resulted in intensive interstitial infiltration and a severe tubular destruction in the cortex. Treatment with hydrocortisone did not prevent PMN migration and tissue damage. By contrast, treatment with L-651,392 resulted in a significant reduction in PMNs (P < 0.001 in comparisons with all other groups) and greater preservation of the tubular structure despite identical bacterial counts than in the group receiving hydrocortisone. We conclude that L-651,392 prevents inflammatory cells from reaching the site of infection and protects the kidney from tubular damage associated with inflammation during pyelonephritis. Inhibitors of leukotrienes should be further investigated for their potential benefit as adjuvants to antibiotherapy in the treatment of pyelonephritis.Several studies support the hypothesis that acute inflammation plays a major role in the development of tissue damage during infection. For example (17,37), the presence of bacteria in the renal parenchyma during pyelonephritis induces a marked local cellular and humoral response. Inflammatory cells such as polymorphonuclear cells (PMNs) migrate into the interstitium under chemotactic stimuli and then release free oxygen radicals (02 -, OH, and H202) and lysosomal enzymes into their environment. Although these products are essential for bacterial killing, they are in part responsible for deleterious effects to host cells, including tissue damage and scar formation, with the ensuing decreased renal function as well as permanent kidney damage.While the C5a fraction of complement may initiate the migration of PMNs in the early phase of the infection (38), the potent chemotactic leukotriene B4 (LTB4) and also the cysteinyl leukotrienes LTC4, -D4, and -E4 are suspected of playing an important role in the outcome of pyelonephritis. Infiltrating leukocytes and cells from the rat glomeruli can produce leukotrienes (2, 11). Their synthesis is stimulated by bacterial components such as endotoxin. Studies of septic shock and different diseases of the lu...

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Section: Discussionsupporting

confidence: 85%

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

Tardif

Beauchamp

Bergeron

et al. 1994

Antimicrob Agents Chemother

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“…The effect of adrenalectomy or glucocorti coid administration may be due to alterations in the synthesis of the receptors. However, since the modifica tions in CRF binding are observed as early as 24 h after adrenalectomy, they could also occur secondarily to 'unco vering' of receptors already present [25]. The direct effect of glucocorticoids on CRF receptors is supported by the dem onstration that glucocorticoids inhibit the development of pituitary desensitization to CRF when tested in vitro, in cultured rat anterior pituitary cells [7], Thus, the lack of pi tuitary desensitization during in vivo administration of CRF [8,27] may be due to the ambient circulating glucocor ticoids.…”

Section: Discussionmentioning

confidence: 99%

Effect of Passive Immunization against Corticotropin-Releasing Factor (CRF) on the Postadrenalectomy Changes of CRF Binding Sites in the Rat Anterior Pituitary Gland

Grino¹,

Guillaume²,

Castanas³

et al. 1987

Neuroendocrinology

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The concentration of corticotropin-releasing factor (CRF)-binding sites decreases in the rat anterior pituitary after adrenalectomy; this change may be related either to a direct effect of the circulating glucocorticoids at the pituitary level or to a desensitization of CRF receptors through an increased CRF release in hypophysial portal blood. In order to examine the latter possibility we have measured plasma adrenocorticotropin hormone (ACTH) levels and the number of anterior pituitary CRF binding sites in sham-operated and 24-hour adrenalectomized rats after blockade of endogenous CRF by passive immunization with an antiserum anti-rat CRF (CRF-AS), or after injection of normal rabbit serum (NRS). In NRS-injected rats, after sham operation, plasma ACTH concentration increased (227 + 34 vs. 118 ± 19 pg/ml in controls) without change in CRF-binding sites capacity (20.7 ± 2.6 vs. 24.6 ± 3.5 fmol/mg protein in controls). Adrenalectomy induced a large rise in plasma ACTH (785 ± 89 pg/ml) and a decrease in the number of CRF-binding sites (12.2 ± 1.7 fmol/mg protein). After CRF-AS injection, plasma ACTH was normalized in sham-operated animals (149 ± 24 pg/ml) and significantly reduced in adrenalectomized rats (472 ± 76 pg/ml); the adrenalectomy-induced decrease in the number of CRF-binding sites was unaffected by the CRF-AS administration (12.2 ± 1.7 fmol/mg protein). The administration of dexamethasone to adrenalectomized rats significantly reduced plasma ACTH concentrations (23.3 ± 10.6 pg/ml) and prevented the loss in CRF-binding sites capacity (20.7 + 1.3 fmol/mg protein). Affinity of CRF for its binding sites was unchanged in all the groups studied. These findings suggest that the postadrenalectomy reduction in the number of anterior pituitary CRF-binding sites may be mainly due to a direct glucocorticoid effect at the pituitary level rather than a consequence of a possible increased CRF secretion.

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“…Glucocorticoids and ceramide synthesis. The discovery that glucocorticoids have a large and specific effect on sphingolipids derived from studies addressing the theory that the broad scope of corticosteroid action was due to the ability of different hormones to directly modify membrane lipids (39). Specifically, the well-recognized importance of corticosteroids in protection against stress was considered to possibly relate to membrane fluidity, which is involved in the adaptation of bacteria, fish, and hibernating animals to extremes of heat and cold (40).…”

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confidence: 99%

A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing’s Syndrome

2005

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Metabolic syndrome X and type 2 diabetes share many metabolic and morphological similarities with Cushing's syndrome, a rare disorder caused by systemic glucocorticoid excess. Pathologies frequently associated with these diseases include insulin resistance, atherosclerosis, susceptibility to infection, poor wound healing, and hypertension. The similarity of the clinical profiles associated with these disorders suggests the influence of a common molecular mechanism for disease onset. Interestingly, numerous studies identify ceramides and other sphingolipids as potential contributors to these sequelae. Herein we review studies demonstrating that aberrant ceramide accumulation contributes to the development of the deleterious clinical manifestations associated with these diseases. Diabetes 54:591-602, 2005

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Corticosteroid-Induced Changes in Phospholipid Membranes as Mediators of Their Action*

Cited by 67 publications

References 195 publications

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis

Effect of Passive Immunization against Corticotropin-Releasing Factor (CRF) on the Postadrenalectomy Changes of CRF Binding Sites in the Rat Anterior Pituitary Gland

A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing’s Syndrome

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