Anti-inflammatory actions of steroids: molecular mechanisms

Barnes, Peter J.; Adcock, Ian M.; Spedding, Michael; Vanhoutte, Paul M.

doi:10.1016/0165-6147(93)90184-l

Cited by 692 publications

(381 citation statements)

References 39 publications

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“…The nuclear receptor-dependent action of glucocorticoids, on the contrary, has been fairly well investigated (Boumpas et al, 1993;Barnes and Adcock, 1993). In general, the classic receptor-mediated action of glucocorticoids results in the increase in the transcriptional rate of certain genes.…”

Section: Discussionmentioning

confidence: 99%

Effects of Steroidal and Non Steroidal Drugs on the Neovascularization Response Induced by Tumoral TA3 Supernatant on CAM from Chick Embryo

Zúñiga¹,

Fuenzalida²,

Guerrero³

et al. 2003

Biol. Res.

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Angiogenesis, the development of new blood vessels from the existing vascular network, may result as a consequence of the increase or decrease of proangiogenic or antiangiogenic factors, respectively. The tumor itself could up-regulate the production of angiogenic factors. Recently, we established that the steroidal drug betamethasone in low concentration inhibit the neovascularization promoted by TA3 Ts on CAM of chick embryos. We describe here the effects of the non-steroidal drug ketoprofen, alone or in association with betamethasone, on the angiogenesis promoted by TA3 Ts on CAM. The main finding reported here is that the formation of new blood vessels is strongly inhibited by low concentrations of ketoprofen. The association of both drugs produced a synergistic effect, significantly decreasing tumoral supernatant angiogenesis. It is known that steroidal anti-inflammatory drugs inhibit the enzymes required for the production of prostaglandins through a nuclear GR mediated mechanism. This may operate as a general mechanism in endothelial cells as well. Considering that the induction of COX 1 and COX2 are inhibited by ketoprofen, and that these enzymes are located in the stromal compartment of the CAM, we propose that its antiangiogenic effect may occur via inhibition of the two COX isoforms. In fact, we found that ketoprofen induced apoptosis in both the stromal fibroblast and endotelial cells. The potentiated effect of the combination of betamethasone and ketoprofen may have some therapeutic projections in the control of pathological angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Effects of Steroidal and Non Steroidal Drugs on the Neovascularization Response Induced by Tumoral TA3 Supernatant on CAM from Chick Embryo

Zúñiga¹,

Fuenzalida²,

Guerrero³

et al. 2003

Biol. Res.

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“…However, little is known about their mechanism(s) or site(s) of action [30,31]. We have shown previously that DEX inhibited eotaxin-induced E infiltration when administered systemically but not locally [10].…”

Section: Discussionmentioning

confidence: 99%

Resident mast cells are important for eotaxin-induced eosinophil accumulation in vivo

Das

Flower

Perretti

1998

Journal of Leukocyte Biology

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Eotaxin administration intraperitoneally, but not into dorsal air-pouches, of ovalbuminsensitized mice exhibiting blood eosinophilia induced a threefold increase in eosinophil (E s) infiltration. Transfer of 1 ؋ 10 6 mixed peritoneal cavity cells (PCC), containing 3.5 to 4.5 ؋ 10 4 mast cells (MC), from donor mice to air-pouches of sensitized (but not unsensitized) recipient mice, established an E infiltration to eotaxin (vehicle, 0.86 ؎ 0.27 ؋ 10 6 ; eotaxin, 1.63 ؎ 0.16 ؋ 10 6 E s/air-pouch). Neutrophil numbers were also increased. When MC-depleted (؊93%) PCC were injected into air-pouches of recipient animals, E infiltration was not supported (؊52%). Injection of macrophage-depleted (؊99%) PCC into airpouches elicited a full E response to eotaxin but not neutrophil infiltration (؊81%). Systemic dexamethasone treatment of recipient mice reduced E accumulation; treatment of donor mice only reduced neutrophil accumulation. Our study points to a crucial role for MC in E recruitment by eotaxin. J. Leukoc. Biol. 64: 156-162; 1998.

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“…A semiselective COX-2 inhibitor (COX-2:COX-1 selectivity ∼10:1; Taro, Haifa Bay, Israel) (25) was dissolved in corn oil and injected s.c. 30 min before surgery, (50 mg/kg, 10 ml/kg). The t 1/2 etodolac is ∼8 h in humans and 16 h in mice (26). Poly(I:C).…”

Section: Drugs and Their Administrationmentioning

confidence: 99%

Improving Survival Rates in Two Models of Spontaneous Postoperative Metastasis in Mice by Combined Administration of a β-Adrenergic Antagonist and a Cyclooxygenase-2 Inhibitor

Glasner

Avraham

Rosenne

et al. 2010

The Journal of Immunology

219

177

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Clinical practice does not consider perioperative paracrine and neuroendocrine stress responses as risk factors for cancer recurrence, although recent animal studies provided supportive evidence. Suggested mechanisms include the effects of stress-hormones on tumor cells and on host physiology. In this study, in mice undergoing primary tumor excision, we tested the survival-enhancing potential of perioperative blockade of catecholamines and prostaglandins, and studied potential mediating mechanisms. C57BL/6J mice were inoculated intrafootpad with syngeneic B16F10.9-melanoma or Lewis lung carcinoma, and the paw was amputated when a developing tumor exceeded 100 μl. The clinically used β-adrenergic antagonist propranolol, and/or the cyclooxygenase-2 inhibitor etodolac, were administered once before amputation, and recurrence-free survival was monitored. In different studies, NK cytotoxicity, leukocytes' molecular functional markers, and vascular endothelial growth factor secretion by tumor cells were studied in the context of surgery and drug treatments. The findings indicated that the combination of propranolol and etodolac, but neither drug alone, significantly and markedly improved survival rates in both tumor models, and was as effective as established immunostimulatory agents (IL-12 and polyinosinic-polycytiylic acid). Surgery markedly reduced NK cytotoxicity and NK cell expression of Fas ligand and CD11a, reduced all circulating lymphocyte-subtype concentrations, and increased corticosterone levels. Propranolol and etodolac administration counteracted these perturbations. B16 and 3LL secreted vascular endothelial growth factor in vitro, but secretion was not affected by catecholamine agonists, prostaglandins, corticosterone, propranolol, or etodolac. Overall, propranolol and etodolac administration, which could be applied perioperatively in most cancer patients with minimal risk and low cost, has counteracted several immunologic and endocrinologic perturbations and improved recurrence-free survival rates in mice undergoing primary tumor excision.

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Anti-inflammatory actions of steroids: molecular mechanisms

Cited by 692 publications

References 39 publications

Effects of Steroidal and Non Steroidal Drugs on the Neovascularization Response Induced by Tumoral TA3 Supernatant on CAM from Chick Embryo

Effects of Steroidal and Non Steroidal Drugs on the Neovascularization Response Induced by Tumoral TA3 Supernatant on CAM from Chick Embryo

Resident mast cells are important for eotaxin-induced eosinophil accumulation in vivo

Improving Survival Rates in Two Models of Spontaneous Postoperative Metastasis in Mice by Combined Administration of a β-Adrenergic Antagonist and a Cyclooxygenase-2 Inhibitor

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