Glucocorticoid inhibition of RANTES expression in human lung epithelial cells.

Kwon, O Jung; Jose, P J; Robbins, Richard; Schall, Thomas J.; Williams, Timothy J.; Barnes, Peter J.

doi:10.1165/ajrcmb.12.5.7537968

Cited by 119 publications

(71 citation statements)

References 30 publications

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“…One such gene codes for the proinflammatory cytokine RANTES, which is positively regulated by TNF-␣ in A549 cells. 20,21 Thus, A549 cells were transfected with the expression vector for the wildtype GR (pCIGR) or for the hormone-binding and transactivation-deficient mutant (pCINA). Cells transfected with the empty vector and treated with TNF-␣ produced the highest amount of RANTES.…”

Section: Figure 4 Repression Of Nf-b Activity By Overexpression Of Thmentioning

confidence: 99%

“…[32][33][34] Importantly, the negative regulation of AP-1 and NF-B activities by the hormone-free GR affected the expression of transfected reporter genes but also that of an endogenous gene which is involved in the pathophysiology of asthma, 35 contains AP-1 and NF-B sites, 20 and is induced by the physiological ligand TNF-␣. 21,36 This gene encodes the proinflammatory cytokine RANTES which is chemotactic for monocytes, T cells and eosinophils. [37][38][39] Although the maximal fraction of A549 cells that could be transfected was estimated to be 50%, an 80% drop in RANTES production was observed.…”

Section: Figure 7 Inhibition Of Rantes Production By Overexpression Omentioning

confidence: 99%

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The glucocorticoid receptor gene as a candidate for gene therapy in asthma

et al. 1999

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Glucocorticoids (GC) are commonly used as anti-inflamexpression vector. Using AP-1 and NF-B-dependent matory drugs in asthma, but can produce serious secondreporter gene assays and an immunoassay for the proary effects and, moreover, be inefficient in corticoresistant inflammatory cytokine RANTES, we show that the overasthmatics. After binding to the glucocorticoid receptor expressed GR significantly repressed AP-1 and NF-B (GR), they repress the synthesis of proinflammatory cytoactivities in the absence of hormone and that the GC kines via inhibition of the transcription factors AP-1 and NFdexamethasone produced an additive inhibitory effect. The B. Since qualitative and quantitative defects of the GR GC-independent repression of AP-1 and NF-B activities have been reported in corticoresistant patients, the transfer was further demonstrated by overexpressing a ligandof the GR gene in the lung epithelium, the primary site of binding deficient GR mutant. Our data suggest that delivery inflammation in asthma, may restore sensitivity to GC in of the GR gene in vivo may reduce inflammation without these patients. As a prerequisite to in vivo studies, we have recourse to GC and may constitute an alternative theratransfected A549 human lung epithelial cells with a GR peutic approach for corticoresistant asthma.

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Section: Figure 4 Repression Of Nf-b Activity By Overexpression Of Thmentioning

confidence: 99%

Section: Figure 7 Inhibition Of Rantes Production By Overexpression Omentioning

confidence: 99%

The glucocorticoid receptor gene as a candidate for gene therapy in asthma

et al. 1999

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“…Dexamethasone decreased TNF-α-induced RANTES mRNA expression and RANTES production in A549 cells [50]. This could be expected to reduce eosinophil recruitment by the epithelium, and may be an important target for corticosteroid therapy in asthma [50].…”

Section: Glucocorticosteroidsmentioning

confidence: 92%

“…RANTES is not expressed by the human lung epithelial cell line (A549) under basal conditions [50]. However, stimulation with IL-1 or TNF (but not IL-2, IL-4, IL-6, GM-CSF or IFN-γ) induced RANTES messenger ribonucleic acid (mRNA) expression and protein production in a time-and concentration-dependent manner [50].…”

Section: Epithelial Cytokines/chemokinesmentioning

confidence: 99%

Proinflammatory potential of the airway epithelium in bronchial asthma

Raeburn¹,

Webber²

1994

Eur Respir J

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P Pr ro oi in nf fl la am mm ma at to or ry y p po ot te en nt ti ia al l o of f t th he e a ai ir rw wa ay y e ep pi it th he el li iu um m i in n b br ro on nc ch hi ia al l a as st th hm ma a The epithelium has been suggested to be a target for inflammatory cell mediators and cytokines. Recently, the airway epithelium has itself been shown to produce and release several proinflammatory mediators and cytokines, and to express adhesion molecules for inflammatory cells. The epithelium, thus, may actively participate in the inflammatory changes in asthma, where it may be a source as well as a target.Drug therapy aimed at preventing inflammatory changes in the epithelium, such as cytokine and adhesion molecule expression, may be an important step forward in halting disease progression in asthma.

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“…Although corticosteroids are known to inhibit the expression of RANTES in bronchial epithelial cells (11,12) and airway smooth muscle cells (13) through a process involving interaction of glucocorticoid receptors with the transcription factor NF-B and AP-1 (14), little is known about their effect on IL-16.…”

mentioning

confidence: 99%

Role of B7-CD28/CTLA-4 Costimulation and NF-κB in Allergen-Induced T Cell Chemotaxis by IL-16 and RANTES

Hidi

Riches

Al-Ali

et al. 2000

The Journal of Immunology

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The mechanisms that cause T cell recruitment into inflamed airways of asthmatic individuals are poorly understood. It has been shown previously that both natural exposure to allergen and challenge in the laboratory induce T cell accumulation in the bronchial mucosa of sensitized asthmatics. To study the mechanisms involved in this process, we have used an explant model in which bronchial biopsies taken from mild atopic asthmatic volunteers during fiberoptic bronchoscopy were stimulated in culture for 24 h by the common aeroallergen house dust mite (Dermatophagoides pteronyssinus (Der p)). Analysis of culture supernatants showed that stimulation with Der p significantly enhanced both the generation of T cell chemotactic activity by the mucosal tissue, as assayed in microchemotaxis chambers, and the production of IL-16 and RANTES. Neutralization experiments showed that IL-16 contributed more to the chemotactic activity than RANTES. The fusion protein CTLA-4-Ig, blocking B7:CD28 costimulation, and dexamethasone both significantly reduced the ex vivo production of chemotactic activity and release of IL-16 and RANTES. The proteasome inhibitor Cbz-Ile-Glu(OtBu)-Ala-leucinal also had a significant inhibitory effect on T cell chemotactic activity and IL-16 but not RANTES generation, indicating a role for nuclear factor NFκB activation. These results indicate that allergen stimulates cells within the bronchial mucosa to increase IL-16 and RANTES release, both of which contribute to T cell accumulation in asthmatic airways. The allergen-induced chemotactic activity is dependent on cell activation via CD28 and involves, at least partly, NF-κB.

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Glucocorticoid inhibition of RANTES expression in human lung epithelial cells.

Cited by 119 publications

References 30 publications

The glucocorticoid receptor gene as a candidate for gene therapy in asthma

The glucocorticoid receptor gene as a candidate for gene therapy in asthma

Proinflammatory potential of the airway epithelium in bronchial asthma

Role of B7-CD28/CTLA-4 Costimulation and NF-κB in Allergen-Induced T Cell Chemotaxis by IL-16 and RANTES

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