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Titolo:
Cross-talk between pro-inflammatory transcription factors and glucocorticoids
Autore:
Adcock, IM; Caramori, G;
Indirizzi:
Natl Heart & Lung Inst, Imperial Coll Sch Sci Technol & Med, London SW3 6LY, England Natl Heart & Lung Inst London England SW3 6LY d, London SW3 6LY, England
Titolo Testata:
IMMUNOLOGY AND CELL BIOLOGY
fascicolo: 4, volume: 79, anno: 2001,
pagine: 376 - 384
SICI:
0818-9641(200107)79:4<376:CBPTFA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; FACTOR-KAPPA-B; RESISTANT BRONCHIAL-ASTHMA; N-TERMINAL KINASE; C-FOS EXPRESSION; MOLECULAR MECHANISMS; DNA-BINDING; GENE-REGULATION; FACTOR-ALPHA; IN-VIVO;
Keywords:
acetylation; AP-1; asthma; glucocorticoid; histones; inflammation; NF-kappa B; receptors; transcription factor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Adcock, IM Natl Heart & Lung Inst, Imperial Coll Sch Sci Technol & Med, Dovehouse St,London SW3 6LY, England Natl Heart & Lung Inst Dovehouse St London England SW3 6LY and
Citazione:
I.M. Adcock e G. Caramori, "Cross-talk between pro-inflammatory transcription factors and glucocorticoids", IMM CELL B, 79(4), 2001, pp. 376-384

Abstract

Asthma is a chronic inflammatory disease of the airway that is characterized by cellular infiltration and activation. These processes are induced by overexpression of chemokines and cytokines, such as eotaxin, IL-1 beta and GM-CSF. These mediators are downstream targets for the transcription factors activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), which control the expression of most immunomodulatory genes and whose activity andexpression are elevated in asthma. Glucocorticoids are the most effective anti-inflammatory drugs used in the treatment of chronic inflammatory diseases such as asthma. They act by binding to a specific glucocorticoid receptor (GR) that on activation translocates to the nucleus and either increases(transactivates) or decreases (transrepresses) the expression of responsive genes. Transrepression is the major mechanism of glucocorticoid action ininhibiting inflammatory gene expression. Thus, the ability of the transciption factors AP-1 and NF-kappaB to induce gene transcription is attenuated by GR. Although only 5-10% of asthmatic subjects are glucocorticoid-insensitive, these subjects account for over 50% of the health-care costs for asthma (> $6 billion per annum). Examining these patients also gives an insightinto important aspects of glucocorticoid action in controlling inflammation and into the development of potential new drugs. Biochemical and genomic studies have indicated abnormal induction of the c-Jun N-terminal kinase (JNK) pathway in some of these patients. The ability of most patients to respond to dexamethasone with induction of histone acetylation correlated with nuclear translocation of GR. However, a subgroup of these patients had an inability to correctly interact with the basal transcription complex in spite of high levels of nuclear GR. This suggests that cross-talk between pro- and anti-inflammatory transcription factors may modulate activation of the transcriptional complex and thereby reduce steroid actions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 04:39:28