Glucocorticoid-mediated repression of nuclear factor-κBdependent transcription involves direct interference with transactivation

Bosscher, Karolien De; Schmitz, M. Lienhard; Berghe, Wim Vanden; Plaisance, Stéphane; Fiers, Walter; Haegeman, Guy

doi:10.1073/pnas.94.25.13504

Cited by 341 publications

(232 citation statements)

References 65 publications

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“…Consistent with this, the protein synthesis inhibitor cycloheximide (CHX) did not diminish the inhibitory effect of dex on expression of IL-6, intracellular adhesion molecule (ICAM)-1 or COX-2 mRNAs (De Bosscher et al, 1997;Wissink et al, 1998). In other studies, CHX blocked the GCmediated suppression of urokinase plasminogen activator, COX-2 and CXCL8 mRNA (Chang et al, 2001;Chaudhary and Avioli, 1996;Chivers et al, 2006;Henderson and Kefford, 1993;Newton et al, 1998;Tobler et al, 1992).…”

Section: Inhibitory Effects Of Gc Do Not Require De Novo Gene Expressmentioning

confidence: 80%

“…In some studies anti-inflammatory effects of GCs were not accompanied by changes in DNA-binding activity of NFκB as measured by electrophoretic mobility shift assay (Brostjan et al, 1996;De Bosscher et al, 1997;Hofmann et al, 1998;Nissen and Yamamoto, 2000;Ray et al, 1997;Wissink et al, 1998). However, in other cases GCs were found to inhibit NFκB activation as measured by the same assay (Eberhardt et al, 2002;Goppelt-Struebe et al, 2000;Kurata and Yamamoto, 1999;Kurokouchi et al, 2000;Ma et al, 2004;Mukaida et al, 1994;Vital et al, 2003).…”

Section: Gc-dependent Inhibition Of Gene Expression Is Not Accompaniementioning

confidence: 99%

“…A number of problems with this hypothesis have since been raised. In several different cell types the GC-induced upregulation of IκBα either did not occur or was not sufficient to alter the degradation of IκBα protein, and the nuclear translocation of NFκB in response to pro-inflammatory stimuli (Adcock et al, 1999;Adcock et al, 1997;Auwardt et al, 1998;Brostjan et al, 1996;De Bosscher et al, 1997;Hofmann et al, 1998;Liden et al, 2000;Nissen and Yamamoto, 2000;Pruett et al, 2003;Ray et al, 1997;Wissink et al, 1998). As described above, inhibition of inflammatory gene expression could occur without apparent changes in NFκB promoter occupancy (Liden et al, 2000;Luecke and Yamamoto, 2005 All of these observations clearly establish that inhibition of NFκB function can occur independently of IκBα induction.…”

Section: A Clarkmentioning

confidence: 99%

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Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

238

193

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Section: Inhibitory Effects Of Gc Do Not Require De Novo Gene Expressmentioning

confidence: 80%

Section: Gc-dependent Inhibition Of Gene Expression Is Not Accompaniementioning

confidence: 99%

Section: A Clarkmentioning

confidence: 99%

See 1 more Smart Citation

Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

238

193

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“…Steroidmediated repression of NF-B-dependent genes has also been demonstrated in fibroblasts, although I B protein levels remained unchanged. It has been suggested that direct protein-protein interactions between the activated glucocorticoid receptor and the p65 subunit of NF-B can mediate suppression of NF-Bdependent transcriptional activity (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects of acetylsalicylic acid in giant cell arteritis

Weyand

Kaiser

Yang

et al. 2002

Arthritis & Rheumatism

141

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Objective. In giant cell arteritis (GCA), inflammatory lesions typically produce interferon-␥ (IFN␥)-and nuclear factor B (NF-B)-dependent monokines. Corticosteroids influence disease activity by repressing NF-B-dependent genes but have only marginal effects on IFN␥. The current study explored whether acetylsalicylic acid (ASA) had cytokine-repressing activity in GCA and could function as a steroid-sparing agent.Methods. Temporal artery-severe combined immunodeficiency (SCID) mouse chimeras were created by engrafting inflamed temporal arteries into SCID mice. Chimeras were treated with ASA, indomethacin, or dexamethasone for 3 weeks. Temporal artery grafts were harvested and cytokine message was semiquantified by polymerase chain reaction-enzyme-linked immunosorbent assay. The ability of dexamethasone and ASA to suppress IFN␥ and interleukin-1␤ (IL-1␤) messenger RNA and protein production was also tested in vitro using T cell clones and monocytes derived from patients with GCA. Drug-induced effects on the transcription factors NF-B and activator protein 1 (AP-1) were assessed by electrophoretic mobility shift assays (EMSAs).Results. At clinically relevant doses, 20-100 mg/kg, ASA was a highly effective inhibitor of cytokine transcription in temporal arteries. While dexamethasone preferentially targeted NF-B-regulated monokines, ASA acted predominantly by suppressing IFN␥. Indomethacin failed to reduce tissue IFN␥ transcription, which therefore excluded the inhibition of cyclooxygenases as a critical mechanism. IFN␥ production by T cell clones was highly sensitive to ASA-mediated suppression, whereas IL-1␤ production by lipopolysaccharide-stimulated monocytes responded primarily to dexamethasone. The combination of ASA and dexamethasone had synergistic effects. EMSAs demonstrated that ASA interfered with the formation of AP-1, whereas dexamethasone suppressed the nuclear translocation of NF-B.Conclusion. The results of this study provide evidence of the complementary action of ASA and corticosteroids in suppressing proinflammatory cytokines in the vascular lesions of GCA.

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“…Several studies have indicated that glucocorticoid receptor activation may repress transcription and/or splicing of NCAM (Colwell et al, 1992;Quandt et al, 1995;De Bosscher et al, 1997;Simpson and Morris, 2000;Datson et al, 2001;Karin and Chang, 2001;Takeuchi and Fukunaga, 2003;Sandi, 2004).…”

Section: Exposure To Stress During Juvenility Alters Emotional Responmentioning

confidence: 99%

Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders

Tsoory

Guterman

Richter‐Levin

2007

Neuropsychopharmacol

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Childhood trauma is associated with higher rates of both mood and anxiety disorders in adulthood. The exposure of rats to stressors during juvenility has comparable effects, and was suggested as a model of induced predisposition for these disorders. The neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM are critically involved in neural development, activity-dependent synaptic plasticity, and learning processes. We examined the effects of exposure to stressors during juvenility on coping with stressors in adulthood and on NCAM and PSA-NCAM expression within the rat limbic system both soon after the exposure and in adulthood. Exposure to stressors during juvenility reduced novel-setting exploration and impaired two-way shuttle avoidance learning in adulthood. Among naive rats, a development-related decrease of about 50% was evident in the PSA-NCAM to NCAM expression ratio in the basolateral amygdala, in the CA1 and dentate gyrus regions of the hippocampus, and in the entorhinal cortex. In juvenile-stressed rats, we found no such decrease, but rather an increase in the polysialylation of NCAM (B50%), evident soon after the exposure to juvenile stress and also in adulthood. Our results suggest that exposure to stressors during juvenility alters the maturation of the limbic system, and potentially underlies the predisposition to exhibit stress-related symptoms in adulthood.

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Glucocorticoid-mediated repression of nuclear factor-κBdependent transcription involves direct interference with transactivation

Cited by 341 publications

References 65 publications

Anti-inflammatory functions of glucocorticoid-induced genes

Anti-inflammatory functions of glucocorticoid-induced genes

Therapeutic effects of acetylsalicylic acid in giant cell arteritis

Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders

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