Lower sensitivity of nasal polyp fibroblasts to glucocorticoid anti-proliferative effects

Pujols, Laura; Fuentes, Mireya; Fernández-Bertolín, Laura; Alobid, Isam; Roca‐Ferrer, Jordi; Mullol, Joaquim; Picado, César

doi:10.1016/j.rmed.2010.08.001

Cited by 13 publications

(19 citation statements)

References 33 publications

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“…We therefore investigated whether MG262 also reduced collagen expression in nasal fibroblasts. In agreement with our previous studies (Pujols et al, 2011), the profibrogenic stimulus TGF-␤ (5 ng/ml) induced the mRNA expression of collagens 1␣1, 1␣2, and 3␣1 in both nasal mucosa and polyp fibroblasts (Fig. 6A).…”

Section: Resultssupporting

confidence: 93%

“…Patients with nasal polyps and associated asthma have increased fibroblast proliferation and extracellular matrix deposition and increased fibroblast differentiation into myofibroblasts (Pawliczak et al, 2005). Collagens I and III are expressed by lung (Goulet et al, 2007) and nasal fibroblasts (Pujols et al, 2011), and their expression is induced by the profibrotic stimulus transforming growth factor-␤ (TGF-␤).…”

Section: Introductionmentioning

confidence: 99%

“…Nasal polyp fibroblasts also release a variety of cytokines, chemokines, and other proinflammatory mediators, including interleukin (IL)-6, IL-8, granulocyte/macrophage colonystimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and regulated on activation normal T cell expressed and secreted (RANTES), that recruit and activate inflammatory cells into the nasal polyp site, thus contributing to the perpetuation of inflammatory and fibrotic processes in the tissue (Xing et al, 1993;Pujols et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…None of the patients had suffered from upper respiratory infection for at least 2 weeks before surgery. The diagnosis of nasal polyposis and asthma was based on established criteria as reported previously (Pujols et al, 2011). All subjects agreed to participate in the study, which was approved by the Ethics Committee of Hospital Clínic, Barcelona, Spain.…”

Section: Introductionmentioning

confidence: 99%

“…Fragments (approximately 3 ϫ 3 mm) of the nasal tissues were placed in six-well culture dishes in DMEM supplemented with 10% FBS, 100 U/ml penicillin, 100 g/ml streptomycin, and 2 g/ml amphotericin B, in a humidified atmosphere at 37°C and 5% CO 2 . Fibroblasts were isolated from the tissue fragments through adhesion and migration on the plastic surface and further characterized by immunostaining of cytokeratin and vimentin as reported previously (Pujols et al, 2011). In all experiments, cells were growth-arrested by incubation with serum-free medium for 18 to 24 h before drug incubation.…”

Section: Introductionmentioning

confidence: 99%

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Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Pujols

Fernández-Bertolín²,

Fuentes³

et al. 2012

J Pharmacol Exp Ther

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Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflammatory and antifibrotic effects on animal models of various inflammatory and fibrotic diseases. Their effects in cells from patients affected by either inflammatory or fibrotic diseases have been poorly investigated. Nasal polyposis is a chronic inflammatory disease of the sinus mucosa characterized by tissue inflammation and remodeling. We tested the hypothesis that proteasome inhibition of nasal polyp fibroblasts might reduce their proliferation and inflammatory and fibrotic response. Accordingly, we investigated the effect of the proteasome inhibitor Z-Leu-Leu-Leu-B(OH) 2 (MG262) on cell viability and proliferation and on the production of collagen and inflammatory cytokines in nasal polyp and nasal mucosa fibroblasts obtained from surgery specimens. MG262 reduced the viability of nasal mucosa and polyp fibroblasts concentration-and time-dependently, with marked effects after 48 h of treatment. The proteasome inhibitor bortezomib provoked a similar effect. MG262-induced cell death involved loss of mitochondrial membrane potential, caspase-3 and poly(ADP-ribose) polymerase activation, induction of c-Jun phosphorylation, and mitogen-activated protein kinase phosphatase-1 expression. Low concentrations of MG262 provoked growth arrest, inhibited DNA replication and retinoblastoma phosphorylation, and increased expression of the cell cycle inhibitors p21 and p27. MG262 concentrationdependently inhibited basal and transforming growth factor-␤-induced collagen mRNA expression and interleukin (IL)-1␤-induced production of IL-6, IL-8, monocyte chemoattractant protein-1, regulated on activation normal T cell expressed and secreted, and granulocyte/macrophage colony-stimulating factor in both fibroblast types. MG262 inhibited IL-1␤/tumor necrosis factor-␣-induced activation of nuclear factor-B. We conclude that noncytotoxic treatment with MG262 reduces the proliferative, fibrotic, and inflammatory response of nasal fibroblasts, whereas high MG262 concentrations induce apoptosis.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Pujols

Fernández-Bertolín²,

Fuentes³

et al. 2012

J Pharmacol Exp Ther

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Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis

Taylor

Schlosser

Soler

et al. 2018

Int Forum Allergy Rhinol

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Bone Marrow and Adipose-Derived Mesenchymal Stem Cells Alleviate Methotrexate-Induced Pulmonary Fibrosis in Rat: Comparison with Dexamethasone

Fikry

Safar

Hasan

et al. 2015

J Biochem Mol Toxicol

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The present study examined the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in methotrexate (MTX)-induced pulmonary fibrosis in rats as compared with dexamethasone (Dex). MTX (14 mg/kg, as a single dose/week for 2 weeks, p.o.) induced lung fibrosis as marked by elevation of relative lung weight, malondialdehyde, nitrite/nitrate, interleukin-4, transforming growth factor-β1, deposited collagen, as well as increased expression of Bax along with the reduction of reduced glutathione content and superoxide dismutase activity. These deleterious effects were antagonized after treatment either with BM-MSCs or AD-MSCs (2 × 10(6) cells/rat) 2 weeks after MTX to even a better extent than Dex (0.5 mg/kg/ for 7 days, p.o.). In conclusion, BM-MSC and AD-MSCs possessed antioxidant, antiapoptotic, as well as antifibrotic effects, which will probably introduce them as remarkable candidates for the treatment of pulmonary fibrosis.

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Lower sensitivity of nasal polyp fibroblasts to glucocorticoid anti-proliferative effects

Abstract: This impaired sensitivity of nasal polyp fibroblasts to in vitro glucocorticoid effects concurs in part with the poor clinical response that these nasal polyp patients show to glucocorticoid treatment.

Cited by 13 publications

References 33 publications

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Proteasome Inhibition Reduces Proliferation, Collagen Expression, and Inflammatory Cytokine Production in Nasal Mucosa and Polyp Fibroblasts

Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis

Bone Marrow and Adipose-Derived Mesenchymal Stem Cells Alleviate Methotrexate-Induced Pulmonary Fibrosis in Rat: Comparison with Dexamethasone

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