The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone

Tsurufuji, Susumu; Sugio, Kazuo; Takemasa, Fumihiko

doi:10.1038/280408a0

Cited by 212 publications

(96 citation statements)

References 17 publications

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“…The doses of the protein synthesis inhibitor, cycloheximide, used in the present study proved capable in other workers' hands of blocking some of the anti-inflammatory properties of dexamethasone (Tsurufuji et al, 1979;1980). This observation is consistent with the known mechanism of action of steroids in many systems, i.e.…”

Section: Discussionmentioning

confidence: 85%

“…Although 10 and 3 mg/kg subcutaneously were consistently active, the effect of 1 mg/kg was variable. Thus, it was not possible to reproduce the conditions of Tsurufuji et al (1979;1980). Since a glucocorticoidinduced protein with the ability to inhibit phospholipase A2 has been identified and partially characterized (Flower & Blackwell, 1979;Carnuccio et al, 1980;Hirata et al, 1980;Blackwell, Carnuccio, DiRosa, Flower, Parente & Persico, 1980), the first of these possibilities seems to be excluded.…”

Section: Discussionmentioning

confidence: 99%

“…The dose of progesterone used was the same as that found by Tsurufuji et al (1979;1980) to block the antiinflammatory effect of dexamethasone.…”

Section: Effects Of Various Steroids On Endotoxin-induced Diarrhoeamentioning

confidence: 99%

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Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

Doherty¹

1981

British J Pharmacology

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Dexamethasone blocked endotoxin‐induced diarrhoea in mice, but not that induced by arachidonic acid or prostaglandin E2. Indomethacin blocked endotoxin and arachidonic acid‐induced diarrhoea, but not that induced by prostaglandin E2. Codeine blocked all three forms of diarrhoea. The above data, when considered in relation to literature reports that endotoxin induces prostaglandin synthesis, suggest that dexamethasone blocks diarrhoea by preventing the release of arachidonic acid, the substrate for prostaglandin biosynthesis. The activities of indomethacin and dexamethasone in castor oil diarrhoea support the above conclusion and their inactivity in 5‐hydroxytryptophan‐induced diarrhoea confirms the absence of ‘codeine‐like’ direct effects on the gut. Other glucocorticoids (hydrocortisone, prednisolone) were also able to block endotoxin diarrhoea, but oestradiol, testosterone and progesterone did not. The inhibitory action of dexamethasone on endotoxin diarrhoea could not be blocked by the protein synthesis inhibitor, cycloheximide, nor by the glucocorticoid receptor antagonist, progesterone. Thus, involvement of glucocorticoid receptor‐mediated gene activation could not be demonstrated.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

Doherty¹

1981

British J Pharmacology

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“…These effects could be responsible for part of the anti-inflammatory effects of glucocorticosteroids. To support this hypothesis, it has been shown that the anti-inflammatory effects 'Author for correspondence at present address: Dpt of Preventive Medicine, Mass Gen Hospital, Fruit Street, Boston, MA 02114, U.S.A. of glucocorticosteroids involve gene expression and protein synthesis (Tsurufuji et al, 1979) and are correlated with inhibition of eicosanoid production (Parente et al, 1984). Recently, the full cDNA sequence of lipocortin I was obtained (Wallner et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

A purified lipocortin shares the anti‐inflammatory effect of glucocorticosteroids in vivo in mice

Errasfa

Russo‐Marie

1989

British J Pharmacology

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1 The injection of a suspension of a polyacrylamide gel (bio gel) into the dorsal subcutaneous area of mice induced an inflammatory reaction and the migration of neutrophils towards the inflamed site.2 The intravenous administration of anti-inflammatory drugs (dexamethasone, indomethacin and lysine-acetylsalicylate) to polyacrylamide gel-treated mice inhibited the accumulation of neutrophils in the inflamed site. 3 A similar administration of a 36 K mouse lipocortin, induced a strong dose-dependent inhibition of neutrophil accumulation in the inflamed site. 4 Dexamethasone and lipocortin inhibited the production of eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the inflamed site of polyacrylamide gel-treated mice. 5 Lipocortin impaired both phospholipase A2 (PLA2) activity and chemotaxis of isolated inflammatory neutrophils. 6 The present studies show an in vivo anti-inflammatory effect of lipocortin similar to that of glucocorticosteroids. In agreement with recent data on the extracellular effects of various lipocortins, these results might implicate lipocortin(s) in the anti-inflammatory effects of glucocorticosteroids.

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“…Hydrocortisone (HC) and other anti-inflammatory glucocorticoids are not selectively concentrated in inflammed tissues and sometimes induce adverse effects (1 ). On the other hand, numerous workers have reported that the anti-inflammatory actions of glucocorticoids are mediated by the formation of a glucocorticoid-receptor complex, which is transferred into nuclei and induces an anti-inflammatory protein named lipomodulin or macrocortin (2)(3)(4)(5). Recently, we have synthesized a new anti-inflammatory glucocorticoid, hydrocortisone 1 7-butyrate 21 -propionate (HBP), which possesses weak systemic effects and potent topical effects (6).…”

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confidence: 99%

Characteristics of Binding of a New Anti-Inflammatory Glucocorticoid, Hydrocortisone 17-Butyrate 21-Propionate (HBP), to Glucocorticoid Receptors of Rat liver

Murata

Tanaka

Otomo

et al. 1985

Japanese Journal of Pharmacology

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Abstract-Characteristicsof the specific binding of hydrocortisone 17-butyrate 21 -propionate (HBP) to the cytoplasmic fraction from rat liver were investigated. The inhibition constant (K,) of HBP for the site of 3H-dexamethasone (3H-DM) binding was approximately equal to the value of DM and significantly smaller than that of hydrocortisone (HC). The maximum number of binding sites (Borax) and dissociation constant (K,,) for 3H-HBP were also approximately equal to those for 3H-DM . The Scatchard and Hofstee plots analyses of 3H-HC binding indicated that the HC binding sites consisted of three components with different affinity, while that of 3H-DM had only one site with an intermediate affinity. HBP and hydro cortisone 1 7-butyrate (H B) bound to other binding sites of HC in addition to the site for DM. The IC50 value for synthetic glucocorticoids determined from the in hibition curves of 3H-HC binding in the first phase agreed with the values deter mined by the displacement study of 3H-DM binding. Furthermore, the first phase of HBP in the inhibition curve of 3H-HC binding disappeared from the curve, and only the second phase remained following the addition of DM. These results indicate that the esterification of C-17 and C-21 OH increases the affinity of the binding site for synthetic glucocorticoid and attenuates the affinity for the other binding sites of HC.

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The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone

Cited by 212 publications

References 17 publications

Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

A purified lipocortin shares the anti‐inflammatory effect of glucocorticosteroids in vivo in mice

Characteristics of Binding of a New Anti-Inflammatory Glucocorticoid, Hydrocortisone 17-Butyrate 21-Propionate (HBP), to Glucocorticoid Receptors of Rat liver

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