Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells

Romero, Ignacio A.; Radewicz, Katrina; Jubin, Emmanuelle; Michel, C. C.; Greenwood, John; Couraud, Pierre‐Olivier; Adamson, Peter

doi:10.1016/s0304-3940(03)00348-3

Cited by 163 publications

(159 citation statements)

References 19 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…Direct effects of GCs on the BBB were demonstrated in vitro (Figure 2). In cultured brain endothelial cells dexamethasone induced the reduction of pores, the concentration of F-Actin on the cell periphery and an increased expression of ZO-1 and occludin (Förster et al, 2005;Förster et al, 2006;Romero et al, 2003). How these mechanisms impact the integrity of the BBB in vivo requires A c c e p t e d M a n u s c r i p t -10 further investigation.…”

Section: Effects Of Glucocorticoids On the Blood-brain Barrier And Lementioning

confidence: 99%

Glucocorticoids in the control of neuroinflammation

Tischner

Reichardt

2007

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Glucocorticoids are a class of steroid hormones that are endowed with profound antiinflammatory and immunosuppressive activities. Endogenous glucocorticoids are key players in the modulation of the immune system and establish an endocrine basis of many inflammatory diseases. In addition, synthetic glucocorticoids are amongst the most commonly prescribed drugs worldwide for the treatment of autoimmune disorders. In this review we summarize our present knowledge on the mechanisms by which glucocorticoids impact on multiple sclerosis (MS), a highly prevalent neuroinflammatory disease, and its animal model experimental autoimmune encephalomyelitis (EAE). In spite of the new methodologies that have become available during recent years, we are still far from a comprehensive picture of the mechanism by which glucocorticoids control neuroinflammation. Keywords: Glucocorticoids; Multiple Sclerosis; Experimental AutoimmuneEncephalomyelitis; Apoptosis; Blood-brain barrier Page 2 of 33A c c e p t e d M a n u s c r i p t -3 IntroductionGlucocorticoids (GCs) are a class of steroid hormones that are commonly used to treat acute and chronic inflammatory disorders (Tuckermann et al., 2005). They exert most of their functions by binding to the glucocorticoid receptor (GR), which controls gene expression and signalling cascades through genomic as we ll as non-genomic mechanisms. By this means, GCs modulate the survival, differentiation, migration and various effector functions of leukocytes and other cell types and thereby impact both, innate and adaptive immunity. W hilst GCs administered at pharmacological concentrations are considered purely immunosuppressive, fluctuations in the levels of endogenous GCs, e.g. during stress, result in more complex immunomodulatory effects (Elenkov and Chrousos, 1999).One major application of GCs is the treatment of neuroinflammatory disorders, in particular multiple sclerosis (MS), the most prevalent chronic autoimmune disease of the central nervous system (CNS) in the Western world (Noseworthy et al., 2000). MS is characterized by infiltrating autoreactive T-cells in the CNS that initiate aninflammatory cascade involving leukocytes and humoral components (Sospedra and Martin, 2005). This causes demyelination and axonal loss, which eventually leads to severe functional deficits. While GCs have no positive effect on the long-term prognosis of MS, optic neuritis and other acute relapses are widely treated with high doses of methylprednisolone (Milligan et al., 1987). Still, such a therapy may lead to severe complications or incomplete recovery. Furthermore, it is known that the course of MS is influenced by the level of endogenous GCs (Elenkov and Chrousos, 1999). Women in the third trimester of pregnancy and Cushing syndrome patients often experience remission of the disease. This is explained by a polarization of the immune system towards T H 2 dominated responses as a consequence of increased Page 3 of 33A c c e p t e d M a n u s c r i p t -4 cortisol synthesis. Thus, fluctuations in G...

show abstract

Section: Effects Of Glucocorticoids On the Blood-brain Barrier And Lementioning

confidence: 99%

Glucocorticoids in the control of neuroinflammation

Tischner

Reichardt

2007

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

show abstract

“…In other studies, MMP3, -8, and -9 were shown to be able to cleave Occludin, a key protein controlling the tight junction (21)(22)(23). In CNS leukemia, MMP2 and MMP9 secreted by leukemic cells were found to promote the disruption of the tight junction proteins including ZO-1 and Claudin-5, which then increased paracellular permeability of leukemic cells across the BBB (10,24,25). In breast cancer, MMP2 has been shown to be involved in brain metastasis, although the exact role of this metalloproteinase on penetrating BBB is not clear (26).…”

mentioning

confidence: 95%

Roles of the Cyclooxygenase 2 Matrix Metalloproteinase 1 Pathway in Brain Metastasis of Breast Cancer

Fukuda

Xing

et al. 2015

Journal of Biological Chemistry

109

View full text Add to dashboard Cite

Background: Mechanism of brain metastasis of breast cancer is poorly understood. Results: Inflammatory factors secreted from cancer cells degrade tight junction of BBB and stimulate the tumor-microenvironment cross-talk. Conclusion: COX2-prostaglandins-MMP1 pathway promotes brain metastasis by tampering with BBB and up-regulating CCL7 in astrocytes for the growth of tumor initiating cells. Significance: The COX2-prostaglandins-MMP1 pathway may serve as a novel therapeutic target for brain metastasis.

show abstract

“…In addition to the inhibitory effect on cell migration, Dex also induced a rearrangement of the cytoskeleton of SK-N-SH cells; similarly Romero et al (9) have reported that Dex treatment induces changes in the cytoskeleton of cultured rat brain endothelial cells. This effect of Dex has been confirmed by in vivo studies showing that prenatal exposure to Gc brings about modifications of the cell cytoskeleton in the fetal baboon brain (8).…”

Section: Discussionmentioning

confidence: 76%

“…New information on these issues could provide a useful tool for the evaluation of the invasive potential of neuroblastomas. One may hypothesize that changes of motility under the effect of Gc imply a rearrangement of cytoskeleton organization; indeed, reports have been published indicating that Gc affect the morphology and cytoskeleton organization of different cell types (8,9).…”

Section: La Casulari Et Almentioning

confidence: 99%

Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

Casulari¹,

Dondi²,

Maggi³

et al. 2006

Braz J Med Biol Res

View full text Add to dashboard Cite

Glucocorticoids (Gc) influence the differentiation of neural crestderived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1) the presence and the binding characteristics of Gc receptors in these cells, 2) the effect of dexamethasone (Dex) on the migration of SK-N-SH cells, and 3) the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1) receptors that bind [ 3 H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell) are present in cytosolic preparations of SK-N-SH cells, and 2) treatment with Dex (in the range of 10 nM to 1 µM) has an inhibitory effect (from 100% to 74 and 43%, respectively) on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 µM), and 3) as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM) on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 µM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s) of action of Gc on cells originating in the neural crest.

show abstract

Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells

Cited by 163 publications

References 19 publications

Glucocorticoids in the control of neuroinflammation

Glucocorticoids in the control of neuroinflammation

Roles of the Cyclooxygenase 2 Matrix Metalloproteinase 1 Pathway in Brain Metastasis of Breast Cancer

Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

Contact Info

Product

Resources

About